Skip to main content
SpringerLink
Log in

Organism Models: Choosing the Right Model

  • Protocol
  • First Online:
Organism Models of Autism Spectrum Disorders

Part of the book series: Neuromethods ((NM,volume 100))

Abstract

This chapter examines the conditions to develop organism models of disease. It is focused on rare diseases because we demonstrate (Chap. 2) that autism is a common denominator to a set of rare diseases. We define the place of the organism models in the translational strategy. We suggest four criteria to improve the validity of organism models: (1) identical etiology in model and in paragon, (2) similar molecular signature, (3) comparable pathophysiological pathways, and (4) experimental analysis of the model must match clinical observations in paragon. We focus on the consequences of an approach examining together the clinical aspects of the disease and its biological correlates. The requirement for using different species to examine the different facets of a disease is discussed in a tissue-specific strategy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Notes

  1. 1.

    Gene symbol is capitalized and italicized when it refers to Homo sapiens. It is italicized for the other species. A capitalized non-italicized symbol indicates the corresponding protein.

References

  1. Haroutunian V, Pickett J (2007) Autism brain tissue banking. Brain Pathol 17(4):412–421

    PubMed  Google Scholar 

  2. Sinclair AH et al (1990) A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346(6281):240–244

    CAS  PubMed  Google Scholar 

  3. Quintana-Murci L, Fellous M (2001) The human Y chromosome: the biological role of a “functional wasteland”. J Biomed Biotechnol 1(1):18–24

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R (1990) Expression of a candidate sex-determining gene during mouse testis differentiation. Nature 348(6300):450–452

    CAS  PubMed  Google Scholar 

  5. Anagnostou E (2012) Translational medicine: mice and men show the way. Nature 491(7423):196–197

    CAS  PubMed  Google Scholar 

  6. Bukelis I, Porter FD, Zimmerman AW, Tierney E (2007) Smith–Lemli–Opitz syndrome and autism spectrum disorder. Am J Psychiatry 164(11):1655–1661

    PubMed  Google Scholar 

  7. Cohen D et al (2005) Specific genetic disorders and autism: clinical contribution towards their identification. J Autism Dev Disord 35(1):103–116

    PubMed  Google Scholar 

  8. De Clemente V et al (2013) Smith–Lemli–Opitz syndrome: a contribution to the delineation of a cognitive/behavioral phenotype. Minerva Pediatr 65(1):61–69

    PubMed  Google Scholar 

  9. Diaz-Stransky A, Tierney E (2012) Cognitive and behavioral aspects of Smith–Lemli–Opitz syndrome. Am J Med Genet C Semin Med Genet 160C(4):295–300

    PubMed  Google Scholar 

  10. Tierney E et al (2006) Abnormalities of cholesterol metabolism in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet 141B(6):666–668

    PubMed Central  PubMed  Google Scholar 

  11. Tierney E, Nwokoro NA, Kelley RI (2000) Behavioral phenotype of RSH/Smith–Lemli–Opitz syndrome. Ment Retard Dev Disabil Res Rev 6(2):131–134

    CAS  PubMed  Google Scholar 

  12. Tierney E et al (2001) Behavior phenotype in the RSH/Smith–Lemli–Opitz syndrome. Am J Med Genet 98(2):191–200

    CAS  PubMed  Google Scholar 

  13. Rumsey RK et al (2014) Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr 164(5):1147–1151, e1141

    PubMed  Google Scholar 

  14. Verhoeven WM et al (2010) Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. Acta Psychiatr Scand 122(2):162–165

    CAS  PubMed  Google Scholar 

  15. Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A (2013) Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr 102(5):462–470

    PubMed Central  PubMed  Google Scholar 

  16. Wolanczyk T, Banaszkiewicz A, Mierzewska H, Czartoryska B, Zdziennicka E (2000) Hyperactivity and behavioral disorders in Sanfilippo A (mucopolysaccharidosis type IIIA)—case report and review of the literature. Psychiatr Pol 34(5):831–837

    CAS  PubMed  Google Scholar 

  17. Artigas-Pallares J, Gabau-Vila E, Guitart-Feliubadalo M (2005) Syndromic autism: II. Genetic syndromes associated with autism. Rev Neurol 40(Suppl 1):S151–S162

    PubMed  Google Scholar 

  18. Dykens EM, Finucane BM, Gayley C (1997) Brief report: cognitive and behavioral profiles in persons with Smith–Magenis syndrome. J Autism Dev Disord 27(2):203–211

    CAS  PubMed  Google Scholar 

  19. Laje G et al (2010) Autism spectrum features in Smith–Magenis syndrome. Am J Med Genet C Semin Med Genet 154C(4):456–462

    PubMed Central  PubMed  Google Scholar 

  20. Martin SC, Wolters PL, Smith AC (2006) Adaptive and maladaptive behavior in children with Smith–Magenis syndrome. J Autism Dev Disord 36(4):541–552

    PubMed  Google Scholar 

  21. Williams SR et al (2010) Array comparative genomic hybridisation of 52 subjects with a Smith–Magenis-like phenotype: identification of dosage sensitive loci also associated with schizophrenia, autism, and developmental delay. J Med Genet 47(4):223–229

    CAS  PubMed  Google Scholar 

  22. Bonati MT et al (2007) Evaluation of autism traits in Angelman syndrome: a resource to unfold autism genes. Neurogenetics 8(3):169–178

    CAS  PubMed  Google Scholar 

  23. Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet al (2008) The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet 17(1):111–118

    CAS  PubMed  Google Scholar 

  24. Kwasnicka-Crawford DA, Roberts W, Scherer SW (2007) Characterization of an autism-associated segmental maternal heterodisomy of the chromosome 15q11-13 region. J Autism Dev Disord 37(4):694–702

    PubMed  Google Scholar 

  25. Pelc K, Cheron G, Dan B (2008) Behavior and neuropsychiatric manifestations in Angelman syndrome. Neuropsychiatr Dis Treat 4(3):577–584

    PubMed Central  PubMed  Google Scholar 

  26. Peters SU, Beaudet al, Madduri N, Bacino CA (2004) Autism in Angelman syndrome: implications for autism research. Clin Genet 66(6):530–536

    CAS  PubMed  Google Scholar 

  27. Simic M, Turk J (2004) Autistic spectrum disorder associated with partial duplication of chromosome 15; three case reports. Eur Child Adolesc Psychiatry 13(6):389–393

    PubMed  Google Scholar 

  28. Trillingsgaard A, ØStergaard JR (2004) Autism in Angelman syndrome: an exploration of comorbidity. Autism 8(2):163–174

    PubMed  Google Scholar 

  29. Veenstra-VanderWeele J, Gonen D, Leventhal BL, Cook EH Jr (1999) Mutation screening of the UBE3A/E6-AP gene in autistic disorder. Mol Psychiatry 4(1):64–67

    CAS  PubMed  Google Scholar 

  30. Veiga MF, Toralles MB (2002) Neurological manifestation and genetic diagnosis of Angelman, Rett and Fragile-X syndromes. J Pediatr (Rio J) 78(Suppl 1):S55–S62

    Google Scholar 

  31. Veltman MW, Craig EE, Bolton PF (2005) Autism spectrum disorders in Prader–Willi and Angelman syndromes: a systematic review. Psychiatr Genet 15(4):243–254

    PubMed  Google Scholar 

  32. Veltman MW et al (2005) A paternally inherited duplication in the Prader–Willi/Angelman syndrome critical region: a case and family study. J Autism Dev Disord 35(1):117–127

    PubMed  Google Scholar 

  33. Borghgraef M, Fryns JP, Dielkens A, Pyck K, Van den Berghe H (1987) Fragile (X) syndrome: a study of the psychological profile in 23 prepubertal patients. Clin Genet 32(3):179–186

    CAS  PubMed  Google Scholar 

  34. Cianchetti C et al (1991) Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families. Am J Med Genet 40(2):234–243

    CAS  PubMed  Google Scholar 

  35. Cohen IL, Vietze PM, Sudhalter V, Jenkins EC, Brown WT (1991) Effects of age and communication level on eye contact in fragile X males and non-fragile X autistic males. Am J Med Genet 38(2–3):498–502

    CAS  PubMed  Google Scholar 

  36. Einfeld S, Molony H, Hall W (1989) Autism is not associated with the fragile X syndrome. Am J Med Genet 34(2):187–193

    CAS  PubMed  Google Scholar 

  37. Matsuishi T et al (1987) Fragile X syndrome in Japanese patients with infantile autism. Pediatr Neurol 3(5):284–287

    CAS  PubMed  Google Scholar 

  38. Reiss AL, Freund L (1992) Behavioral phenotype of fragile X syndrome: DSM-III-R autistic behavior in male children. Am J Med Genet 43(1–2):35–46

    CAS  PubMed  Google Scholar 

  39. Tranebjaerg L, Kure P (1991) Prevalence of fra(X) and other specific diagnoses in autistic individuals in a Danish county. Am J Med Genet 38(2–3):212–214

    CAS  PubMed  Google Scholar 

  40. Zhang A, Shen CH, Ma SY, Ke Y, El Idrissi A (2009) Altered expression of Autism-associated genes in the brain of Fragile X mouse model. Biochem Biophys Res Commun 379(4):920–923

    CAS  PubMed  Google Scholar 

  41. Al-Mateen M, Philippart M, Shields WD (1986) Rett syndrome. A commonly overlooked progressive encephalopathy in girls. Am J Dis Child 140(8):761–765

    CAS  PubMed  Google Scholar 

  42. Gillberg C (1986) Autism and Rett syndrome: some notes on differential diagnosis. Am J Med Genet Suppl 1:127–131

    CAS  PubMed  Google Scholar 

  43. Gillberg C (1987) Autistic symptoms in Rett syndrome: the first two years according to mother reports. Brain Dev 9(5):499–501

    CAS  PubMed  Google Scholar 

  44. Goutieres F, Aicardi J (1986) Atypical forms of Rett syndrome. Am J Med Genet Suppl 1:183–194

    CAS  PubMed  Google Scholar 

  45. Olsson B (1987) Autistic traits in the Rett syndrome. Brain Dev 9(5):491–498

    CAS  PubMed  Google Scholar 

  46. Olsson B, Rett A (1985) Behavioral observations concerning differential diagnosis between the Rett syndrome and autism. Brain Dev 7(3):281–289

    CAS  PubMed  Google Scholar 

  47. Opitz JM (1986) Rett syndrome: some comments on terminology and diagnosis. Am J Med Genet Suppl 1:27–37

    CAS  PubMed  Google Scholar 

  48. Zappella M (1985) Rett syndrome: a significant proportion of girls affected by autistic behavior. Brain Dev 7(3):307–312

    CAS  PubMed  Google Scholar 

  49. Zoghbi HY, Percy AK, Glaze DG, Butler IJ, Riccardi VM (1985) Reduction of biogenic amine levels in the Rett syndrome. N Engl J Med 313(15):921–924

    CAS  PubMed  Google Scholar 

  50. Capone GT, Grados MA, Kaufmann WE, Bernad-Ripoll S, Jewell A (2005) Down syndrome and comorbid autism-spectrum disorder: characterization using the aberrant behavior checklist. Am J Med Genet A 134(4):373–380

    PubMed  Google Scholar 

  51. Dressler A, Perelli V, Bozza M, Bargagna S (2011) The autistic phenotype in Down syndrome: differences in adaptive behaviour versus Down syndrome alone and autistic disorder alone. Funct Neurol 26(3):151–158

    PubMed Central  PubMed  Google Scholar 

  52. Ghaziuddin M (2000) Autism in Down's syndrome: a family history study. J Intellect Disabil Res 44(Pt 5):562–566

    PubMed  Google Scholar 

  53. Howlin P, Wing L, Gould J (1995) The recognition of autism in children with Down syndrome—implications for intervention and some speculations about pathology. Dev Med Child Neurol 37(5):406–414

    CAS  PubMed  Google Scholar 

  54. Ji NY, Capone GT, Kaufmann WE (2011) Autism spectrum disorder in Down syndrome: cluster analysis of Aberrant Behaviour Checklist data supports diagnosis. J Intellect Disabil Res 55(11):1064–1077

    CAS  PubMed  Google Scholar 

  55. Kaufmann WE et al (2003) Specificity of cerebellar vermian abnormalities in autism: a quantitative magnetic resonance imaging study. J Child Neurol 18(7):463–470

    PubMed  Google Scholar 

  56. Kielinen M, Rantala H, Timonen E, Linna SL, Moilanen I (2004) Associated medical disorders and disabilities in children with autistic disorder: a population-based study. Autism 8(1):49–60

    PubMed  Google Scholar 

  57. Bickel HGJ, Hickmans EM (1953) Influence of phenylalanine intake on phenylketonuria. Lancet 2:812–819

    Google Scholar 

  58. McKinney WT (1977) Biobehavioral models of depression in monkeys. In: Hanin I, Usdin E (eds) Animal models in psychiatry and neurology. Pergamon Press, Oxford, pp 117–126

    Google Scholar 

  59. Robbins TW, Phillips AG, Sahakian BJ (1977) Effects of chlordiazepoxide on tail pinch-induced eating in rats. Pharmacol Biochem Behav 6(3):297–302

    CAS  PubMed  Google Scholar 

  60. Tordjman S et al (2007) Animal models relevant to schizophrenia and autism: validity and limitations. Behav Genet 37(1):61–78

    PubMed  Google Scholar 

  61. Silva AJ, Paylor R, Wehner JM, Tonegawa S (1992) Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science 257(5067):206–211

    CAS  PubMed  Google Scholar 

  62. Silva AJ, Stevens CF, Tonegawa S, Wang Y (1992) Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science 257(5067):201–206

    CAS  PubMed  Google Scholar 

  63. Oberlé I et al (1991) Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science 252(5009):1097–1102

    PubMed  Google Scholar 

  64. Yu S et al (1991) Fragile X genotype characterized by an unstable region of DNA. Science 252(5009):1179–1181

    CAS  PubMed  Google Scholar 

  65. Bakker C, Verheij C, Willemsen R, Vanderhelm R, Oerlemans F, Vermey M, Bygrave A, Hoogeveen AT, Oostra BA, Reyniers E et al (1994) Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium. Cell 78:23–33

    Google Scholar 

  66. Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39(Database issue):D152–D157

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Sayed D, Abdellatif M (2011) MicroRNAs in development and disease. Physiol Rev 91(3):827–887

    CAS  PubMed  Google Scholar 

  68. Hansen KF, Sakamoto K, Wayman GA, Impey S, Obrietan K (2010) Transgenic miR132 alters neuronal spine density and impairs novel object recognition memory. PLoS One 5(11):e15497

    CAS  PubMed Central  PubMed  Google Scholar 

  69. De Sandre-Giovannoli A et al (2003) Lamin a truncation in Hutchinson–Gilford progeria. Science 300(5628):2055

    PubMed  Google Scholar 

  70. Osorio FG et al (2011) Splicing-directed therapy in a new mouse model of human accelerated aging. Sci Transl Med 3(106):106ra107

    PubMed  Google Scholar 

  71. Jamain S et al (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27–29

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Laumonnier F et al (2004) X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 74(3):552–557

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Jamain S et al (2008) Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci U S A 105(5):1710–1715

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Hattori M et al (2000) The DNA sequence of human chromosome 21. Nature 405(6784):311–319

    CAS  PubMed  Google Scholar 

  75. Watanabe H et al (2004) DNA sequence and comparative analysis of chimpanzee chromosome 22. Nature 429(6990):382–388

    CAS  PubMed  Google Scholar 

  76. Korenberg JR et al (1994) Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc Natl Acad Sci U S A 91(11):4997–5001

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Delabar JM et al (1993) Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1(2):114–124

    CAS  PubMed  Google Scholar 

  78. Smith DJ, Rubin EM (1997) Functional screening and complex traits: human 21q22.2 sequences affecting learning in mice. Hum Mol Genet 6(10):1729–1733

    CAS  PubMed  Google Scholar 

  79. Smith DJ et al (1997) Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome. Nat Genet 16(1):28–36

    CAS  PubMed  Google Scholar 

  80. Smith DJ, Zhu Y, Zhang J, Cheng JF, Rubin EM (1995) Construction of a panel of transgenic mice containing a contiguous 2-Mb set of YAC/P1 clones from human chromosome 21q22.2. Genomics 27(3):425–434

    CAS  PubMed  Google Scholar 

  81. Altafaj X et al (2001) Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet 10(18):1915–1923

    CAS  PubMed  Google Scholar 

  82. Liu C, Szurek PF, Yu YE (2011) MICER targeting vectors for manipulating the mouse genome. Methods Mol Biol 693:245–256

    CAS  PubMed  Google Scholar 

  83. Herault Y, Rassoulzadegan M, Cuzin F, Duboule D (1998) Engineering chromosomes in mice through targeted meiotic recombination (TAMERE). Nat Genet 20(4):381–384

    CAS  PubMed  Google Scholar 

  84. Felder B et al (2009) FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome. Am J Med Genet A 149A(5):952–959

    PubMed  Google Scholar 

  85. Leroy C et al (2013) The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients. Eur J Hum Genet 21(6):602–612

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Mazzone L, Ruta L, Reale L (2012) Psychiatric comorbidities in asperger syndrome and high functioning autism: diagnostic challenges. Ann Gen Psychiatry 11(1):16

    PubMed Central  PubMed  Google Scholar 

  87. Mazzone L et al (2012) Brief report: peculiar evolution of autistic behaviors in two unrelated children with brachidactyly-mental retardation syndrome. J Autism Dev Disord 42(10):2202–2207

    PubMed  Google Scholar 

  88. Ingason A et al (2011) Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness. Am J Psychiatry 168(4):408–417

    PubMed Central  PubMed  Google Scholar 

  89. Depienne C et al (2009) Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders. Biol Psychiatry 66(4):349–359

    CAS  PubMed  Google Scholar 

  90. Ingason A et al (2011) Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol Psychiatry 16(1):17–25

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Madrigal I, Rodriguez-Revenga L, Xuncla M, Mila M (2012) 15q11.2 microdeletion and FMR1 premutation in a family with intellectual disabilities and autism. Gene 508(1):92–95

    CAS  PubMed  Google Scholar 

  92. Urraca N et al (2013) The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature. Autism Res 6(4):268–279

    PubMed Central  PubMed  Google Scholar 

  93. Barber JC et al (2013) 16p11.2-p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2. Eur J Hum Genet 21(2):182–189

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Bedoyan JK et al (2010) Duplication 16p11.2 in a child with infantile seizure disorder. Am J Med Genet A 152A(6):1567–1574

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Dittwald P et al (2013) NAHR-mediated copy-number variants in a clinical population: mechanistic insights into both genomic disorders and Mendelizing traits. Genome Res 23(9):1395–1409

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Fernandez BA et al (2010) Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet 47(3):195–203

    PubMed  Google Scholar 

  97. Sanders SJ et al (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70(5):863–885

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Bassuk AG et al (2013) Deletions of 16p11.2 and 19p13.2 in a family with intellectual disability and generalized epilepsy. Am J Med Genet A 161A(7):1722–1725

    PubMed  Google Scholar 

  99. Golzio C et al (2012) KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature 485(7398):363–367

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Grayton HM, Fernandes C, Rujescu D, Collier DA (2012) Copy number variations in neurodevelopmental disorders. Prog Neurobiol 99(1):81–91

    CAS  PubMed  Google Scholar 

  101. Horev G et al (2011) Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. Proc Natl Acad Sci U S A 108(41):17076–17081

    PubMed Central  PubMed  Google Scholar 

  102. Zufferey F et al (2012) A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders. J Med Genet 49(10):660–668

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Ahn K et al (2014) High rate of disease-related copy number variations in childhood onset schizophrenia. Mol Psychiatry 19(5):568–572

    CAS  PubMed  Google Scholar 

  104. Aldinger KA et al (2013) Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet A 161A(1):131–136

    PubMed  Google Scholar 

  105. Chen CP et al (2010) A de novo 7.9 Mb deletion in 22q13.2→qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. Eur J Med Genet 53(5):329–332

    PubMed  Google Scholar 

  106. Denayer A et al (2012) Neuropsychopathology in 7 patients with the 22q13 deletion syndrome: presence of bipolar disorder and progressive loss of skills. Mol Syndromol 3(1):14–20

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Lo-Castro A et al (2009) Association of syndromic mental retardation and autism with 22q11.2 duplication. Neuropediatrics 40(3):137–140

    CAS  PubMed  Google Scholar 

  108. McMichael G et al (2014) Rare copy number variation in cerebral palsy. Eur J Hum Genet 22(1):40–45

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Mukaddes NM, Herguner S (2007) Autistic disorder and 22q11.2 duplication. World J Biol Psychiatry 8(2):127–130

    PubMed  Google Scholar 

  110. Phelan MC (2008) Deletion 22q13.3 syndrome. Orphanet J Rare Dis 3:14

    PubMed Central  PubMed  Google Scholar 

  111. Philippe A et al (2008) Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics 122(2):e376–e382

    PubMed  Google Scholar 

  112. Yang M et al (2012) Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 32(19):6525–6541

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Mouse Genome Sequencing Consortium et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420(6915):520–562

    Google Scholar 

  114. Zeng H et al (2012) Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures. Cell 149(2):483–496

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Miller JA, Horvath S, Geschwind DH (2010) Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways. Proc Natl Acad Sci U S A 107(28):12698–12703

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Kyostila K et al (2012) A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD) machinery. PLoS Genet 8(6):e1002759

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Hooper M, Hardy K, Handyside A, Hunter S, Monk M (1987) HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326(6110):292–295

    CAS  PubMed  Google Scholar 

  118. Kuehn MR, Bradley A, Robertson EJ, Evans MJ (1987) A potential animal model for Lesch–Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326(6110):295–298

    CAS  PubMed  Google Scholar 

  119. Wu CL, Melton DW (1993) Production of a model for Lesch–Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. Nat Genet 3(3):235–240

    CAS  PubMed  Google Scholar 

  120. Hoffmann JA (2003) The immune response of Drosophila. Nature 426(6962):33–38

    CAS  PubMed  Google Scholar 

  121. Yoder JA, Nielsen ME, Amemiya CT, Litman GW (2002) Zebrafish as an immunological model system. Microbes Infect 4(14):1469–1478

    CAS  PubMed  Google Scholar 

  122. Mason RP, Giorgini F (2011) Modeling Huntington disease in yeast: perspectives and future directions. Prion 5(4):269–276

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Tauber E et al (2011) Functional gene expression profiling in yeast implicates translational dysfunction in mutant huntingtin toxicity. J Biol Chem 286(1):410–419

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Le Roy I, Carlier M, Roubertoux PL (2001) Sensory and motor development in mice: genes, environment and their interactions. Behav Brain Res 125(1–2):57–64

    PubMed  Google Scholar 

  125. Mainen ZF, Sejnowski TJ (1995) Reliability of spike timing in neocortical neurons. Science 268(5216):1503–1506

    CAS  PubMed  Google Scholar 

  126. Courtine G et al (2007) Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans? Nat Med 13(5):561–566

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Brodmann K (1909) Vergleichende Lokalisationslehre der Grosshirnrinde. J.A. Barth, Leipzig

    Google Scholar 

  128. Muly EC, Nairn AC, Greengard P, Rainnie DG (2008) Subcellular distribution of the Rho-GEF Lfc in primate prefrontal cortex: effect of neuronal activation. J Comp Neurol 508(6):927–939

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Reep R (1984) Relationship between prefrontal and limbic cortex: a comparative anatomical review. Brain Behav Evol 25(1):5–80

    CAS  PubMed  Google Scholar 

  130. Reep RL, Corwin JV, Hashimoto A, Watson RT (1984) Afferent connections of medial precentral cortex in the rat. Neurosci Lett 44(3):247–252

    CAS  PubMed  Google Scholar 

  131. Stevens HE (2010) Prefrontal cortex: disorders and development. J Am Acad Child Adolesc Psychiatry 49(3):203–204

    PubMed  Google Scholar 

  132. Stevens HE et al (2010) Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J Neurosci 30(16):5590–5602

    CAS  PubMed Central  PubMed  Google Scholar 

  133. Hirst WD et al (2003) Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol Pharmacol 64(6):1295–1308

    CAS  PubMed  Google Scholar 

  134. Saywell V et al (2006) Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism. Biochem Biophys Res Commun 340(3):776–783

    CAS  PubMed  Google Scholar 

  135. Naidu S et al (2001) Neuroimaging studies in Rett syndrome. Brain Dev 23(Suppl 1):S62–S71

    PubMed  Google Scholar 

  136. Roubertoux PL, Carlier M (2010) Mouse models of cognitive disabilities in trisomy 21 (Down syndrome). Am J Med Genet C Semin Med Genet 154C(4):400–416

    PubMed  Google Scholar 

  137. Heisenberg M, Borst A, Wagner S, Byers D (1985) Drosophila mushroom body mutants are deficient in olfactory learning. J Neurogenet 2(1):1–30

    CAS  PubMed  Google Scholar 

  138. Guimera J, Casas C, Estivill X, Pritchard M (1999) Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome. Genomics 57(3):407–418

    CAS  PubMed  Google Scholar 

  139. Guimera J et al (1996) A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet 5(9):1305–1310

    CAS  PubMed  Google Scholar 

  140. Noble D (2004) Modeling the heart. Physiology 19:191–197

    CAS  PubMed  Google Scholar 

  141. Travillian RS, Diatchka K, Judge TK, Wilamowska K, Shapiro LG (2011) An ontology-based comparative anatomy information system. Artif Intell Med 51(1):1–15

    PubMed Central  PubMed  Google Scholar 

  142. Travillian RS, Gennari JH, Shapiro LG (2005) Of mice and men: design of a comparative anatomy information system. AMIA Annu Symp Proc; 2005:734–738

    Google Scholar 

  143. Travillian RS, Rosse C, Shapiro LG (2003) An approach to the anatomical correlation of species through the Foundational Model of Anatomy. AMIA Annu Symp Proc; 2003:669–673

    Google Scholar 

  144. Jackson JF, North ER 3rd, Thomas JG (1976) Clinical diagnosis of Down's syndrome. Clin Genet 9(5):483–487

    CAS  PubMed  Google Scholar 

  145. Carlier M et al (2011) Laterality preference and cognition: cross-syndrome comparison of patients with trisomy 21 (Down), del7q11.23 (Williams–Beuren) and del22q11.2 (DiGeorge or Velo-Cardio-Facial) syndromes. Behav Genet 41(3):413–422

    PubMed  Google Scholar 

  146. Collins RT 2nd (2013) Cardiovascular disease in Williams syndrome. Circulation 127(21):2125–2134

    PubMed  Google Scholar 

  147. Fisch GS et al (2012) Developmental trajectories in syndromes with intellectual disability, with a focus on Wolf–Hirschhorn and its cognitive-behavioral profile. Am J Intellect Dev Disabil 117(2):167–179

    PubMed  Google Scholar 

  148. Kececioglu D, Kotthoff S, Vogt J (1993) Williams–Beuren syndrome: a 30-year follow-up of natural and postoperative course. Eur Heart J 14(11):1458–1464

    CAS  PubMed  Google Scholar 

  149. Roubertoux PL, Kerdelhue B (2006) Trisomy 21: from chromosomes to mental retardation. Behav Genet 36(3):346–354

    PubMed  Google Scholar 

  150. Seregaza Z, Roubertoux PL, Jamon M, Soumireu-Mourat B (2006) Mouse models of cognitive disorders in trisomy 21: a review. Behav Genet 36(3):387–404

    PubMed  Google Scholar 

  151. Gogos JA et al (1999) The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat Genet 21(4):434–439

    CAS  PubMed  Google Scholar 

  152. Ronald A, Edelson LR, Asherson P, Saudino KJ (2010) Exploring the relationship between autistic-like traits and ADHD behaviors in early childhood: findings from a community twin study of 2-year-olds. J Abnorm Child Psychol 38(2):185–196

    PubMed Central  PubMed  Google Scholar 

  153. Alarcon M, Yonan AL, Gilliam TC, Cantor RM, Geschwind DH (2005) Quantitative genome scan and Ordered-Subsets Analysis of autism endophenotypes support language QTLs. Mol Psychiatry 10(8):747–757

    CAS  PubMed  Google Scholar 

  154. Richtsmeier JT, Baxter LL, Reeves RH (2000) Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. Dev Dyn 217(2):137–145

    CAS  PubMed  Google Scholar 

  155. Collins RL (1968) On the inheritance of handedness. I. Laterality in inbred mice. J Hered 59(1):9–12

    CAS  PubMed  Google Scholar 

  156. Yamada M et al (2009) Inhibition of calpain increases LIS1 expression and partially rescues in vivo phenotypes in a mouse model of lissencephaly. Nat Med 15(10):1202–1207

    CAS  PubMed Central  PubMed  Google Scholar 

  157. Radyushkin K et al (2009) Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav 8(4):416–425

    CAS  PubMed  Google Scholar 

  158. Scattoni ML, Gandhy SU, Ricceri L, Crawley JN (2008) Unusual repertoire of vocalizations in the BTBR T+tf/J mouse model of autism. PLoS One 3(8):e3067

    PubMed Central  PubMed  Google Scholar 

  159. Scattoni ML et al (2008) Reduced ultrasonic vocalizations in vasopressin 1b knockout mice. Behav Brain Res 187(2):371–378

    CAS  PubMed Central  PubMed  Google Scholar 

  160. Sutherland GR et al (1991) Hereditary unstable DNA: a new explanation for some old genetic questions? Lancet 338(8762):289–292

    CAS  PubMed  Google Scholar 

  161. Madisen L et al (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat Neurosci 15(5):793–802

    CAS  PubMed Central  PubMed  Google Scholar 

  162. Madisen L et al (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13(1):133–140

    CAS  PubMed Central  PubMed  Google Scholar 

  163. Song G, Li Q, Long Y, Hackett PB, Cui Z (2012) Effective expression-independent gene trapping and mutagenesis mediated by Sleeping Beauty transposon. J Genet Genomics 39(9):503–520

    CAS  PubMed  Google Scholar 

  164. Taniguchi H et al (2011) A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71(6):995–1013

    CAS  PubMed Central  PubMed  Google Scholar 

  165. Zhuang X, Masson J, Gingrich JA, Rayport S, Hen R (2005) Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods 143(1):27–32

    CAS  PubMed  Google Scholar 

  166. Farook MF et al (2012) Altered serotonin, dopamine and norepinepherine levels in 15q duplication and Angelman syndrome mouse models. PLoS One 7(8):e43030

    CAS  PubMed Central  PubMed  Google Scholar 

  167. Kato TA et al (2013) Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry. Curr Med Chem 20(3):331–344

    CAS  PubMed  Google Scholar 

  168. Staal WG, de Krom M, de Jonge MV (2012) Brief report: the dopamine-3-receptor gene (DRD3) is associated with specific repetitive behavior in autism spectrum disorder (ASD). J Autism Dev Disord 42(5):885–888

    PubMed Central  PubMed  Google Scholar 

  169. Harrington RA, Lee LC, Crum RM, Zimmerman AW, Hertz-Picciotto I (2013) Serotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy. Autism Res 6(3):149–168

    PubMed  Google Scholar 

  170. Moore SW (2011) Hirschsprung's disease and the brain. Pediatr Surg Int 27(4):347–352

    CAS  PubMed  Google Scholar 

  171. Zhang Y, Kim TH, Niswander L (2012) Phactr4 regulates directional migration of enteric neural crest through PP1, integrin signaling, and cofilin activity. Genes Dev 26(1):69–81

    PubMed Central  PubMed  Google Scholar 

  172. Zhang Y, Niswander L (2012) Phactr4: a new integrin modulator required for directional migration of enteric neural crest cells. Cell Adh Migr 6(5):419–423

    PubMed Central  PubMed  Google Scholar 

  173. Dutton KA et al (2001) Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates. Development 128(21):4113–4125

    CAS  PubMed  Google Scholar 

  174. Elworthy S, Pinto JP, Pettifer A, Cancela ML, Kelsh RN (2005) Phox2b function in the enteric nervous system is conserved in zebrafish and is sox10-dependent. Mech Dev 122(5):659–669

    CAS  PubMed  Google Scholar 

  175. Spanier B, Sturzenbaum SR, Holden-Dye LM, Baumeister R (2005) Caenorhabditis elegans neprilysin NEP-1: an effector of locomotion and pharyngeal pumping. J Mol Biol 352(2):429–437

    CAS  PubMed  Google Scholar 

  176. Kishino T, Lalande M, Wagstaff J (1997) UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 15(1):70–73

    CAS  PubMed  Google Scholar 

  177. Jay V, Becker LE, Chan FW, Perry TL Sr (1991) Puppet-like syndrome of Angelman: a pathologic and neurochemical study. Neurology 41(3):416–422

    CAS  PubMed  Google Scholar 

  178. Sato M, Stryker MP (2010) Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a. Proc Natl Acad Sci U S A 107(12):5611–5616

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Lu Y et al (2009) The Drosophila homologue of the Angelman syndrome ubiquitin ligase regulates the formation of terminal dendritic branches. Hum Mol Genet 18(3):454–462

    CAS  PubMed Central  PubMed  Google Scholar 

  180. Kaufmann WE, MacDonald SM, Altamura CR (2000) Dendritic cytoskeletal protein expression in mental retardation: an immunohistochemical study of the neocortex in Rett syndrome. Cereb Cortex 10(10):992–1004

    CAS  PubMed  Google Scholar 

  181. Chen RZ, Akbarian S, Tudor M, Jaenisch R (2001) Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27(3):327–331

    CAS  PubMed  Google Scholar 

  182. Stuss DP, Boyd JD, Levin DB, Delaney KR (2012) MeCP2 mutation results in compartment-specific reductions in dendritic branching and spine density in layer 5 motor cortical neurons of YFP-H mice. PLoS One 7(3):e31896

    CAS  PubMed Central  PubMed  Google Scholar 

  183. Vonhoff F, Williams A, Ryglewski S, Duch C (2012) Drosophila as a model for MECP2 gain of function in neurons. PLoS One 7(2):e31835

    CAS  PubMed Central  PubMed  Google Scholar 

  184. Marshak S, Meynard MM, De Vries YA, Kidane AH, Cohen-Cory S (2012) Cell-autonomous alterations in dendritic arbor morphology and connectivity induced by overexpression of MeCP2 in Xenopus central neurons in vivo. PLoS One 7(3):e33153

    CAS  PubMed Central  PubMed  Google Scholar 

  185. Sullivan T et al (1999) Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147(5):913–920

    CAS  PubMed Central  PubMed  Google Scholar 

  186. Kubben N et al (2011) Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. Nucleus 2(3):195–207

    PubMed Central  PubMed  Google Scholar 

  187. Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL (2003) A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423(6937):298–301

    CAS  PubMed  Google Scholar 

  188. Arimura T et al (2005) Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum Mol Genet 14(1):155–169

    CAS  PubMed  Google Scholar 

  189. Worman HJ, Gundersen GG (2006) Here come the SUNs: a nucleocytoskeletal missing link. Trends Cell Biol 16(2):67–69

    CAS  PubMed  Google Scholar 

  190. Mounkes LC, Kozlov SV, Rottman JN, Stewart CL (2005) Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice. Hum Mol Genet 14(15):2167–2180

    CAS  PubMed  Google Scholar 

  191. Yang SH et al (2011) Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin. Hum Mol Genet 20(3):436–444

    CAS  PubMed Central  PubMed  Google Scholar 

  192. Varga R et al (2006) Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci U S A 103(9):3250–3255

    CAS  PubMed Central  PubMed  Google Scholar 

  193. Sagelius H et al (2008) Targeted transgenic expression of the mutation causing Hutchinson–Gilford progeria syndrome leads to proliferative and degenerative epidermal disease. J Cell Sci 121(Pt 7):969–978

    CAS  PubMed  Google Scholar 

  194. Wang Y et al (2008) Epidermal expression of the truncated prelamin A causing Hutchinson–Gilford progeria syndrome: effects on keratinocytes, hair and skin. Hum Mol Genet 17(15):2357–2369

    CAS  PubMed Central  PubMed  Google Scholar 

  195. Fong LG et al (2006) Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest 116(3):743–752

    CAS  PubMed Central  PubMed  Google Scholar 

  196. Yang SH et al (2008) Eliminating the synthesis of mature lamin A reduces disease phenotypes in mice carrying a Hutchinson–Gilford progeria syndrome allele. J Biol Chem 283(11):7094–7099

    CAS  PubMed  Google Scholar 

  197. Davies BS, Fong LG, Yang SH, Coffinier C, Young SG (2009) The posttranslational processing of prelamin A and disease. Annu Rev Genomics Hum Genet 10:153–174

    CAS  PubMed Central  PubMed  Google Scholar 

  198. Davies BS et al (2010) An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Hum Mol Genet 19(13):2682–2694

    CAS  PubMed Central  PubMed  Google Scholar 

  199. Coffinier C, Fong LG, Young SG (2010) LINCing lamin B2 to neuronal migration: growing evidence for cell-specific roles of B-type lamins. Nucleus 1(5):407–411

    PubMed Central  PubMed  Google Scholar 

  200. Odgren PR et al (2010) Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies. PLoS One 5(4):e9959

    PubMed Central  PubMed  Google Scholar 

  201. Wojtanik KM et al (2009) The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation. J Lipid Res 50(6):1068–1079

    CAS  PubMed Central  PubMed  Google Scholar 

  202. Bertrand AT et al (2012) DelK32-lamin A/C has abnormal location and induces incomplete tissue maturation and severe metabolic defects leading to premature death. Hum Mol Genet 21(5):1037–1048

    CAS  PubMed  Google Scholar 

  203. Poitelon Y et al (2012) Behavioral and molecular exploration of the AR-CMT2A mouse model Lmna (R298C/R298C). Neuromolecular Med 14(1):40–52

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Aix Marseille Université Inserm, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, 27 Bd. Jean Moulin, 13385, Marseille cedex 5, France

    Nicolas Lévy & Pierre L. Roubertoux

  2. INSERM, UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, 27 Bd. Jean Moulin, 13385, Marseille cedex 5, France

    Nicolas Lévy & Pierre L. Roubertoux

  3. AP-HM, Département de Génétique Médicale, Hôpital d’enfants Timone, Marseille, France

    Nicolas Lévy

Authors
  1. Nicolas Lévy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierre L. Roubertoux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolas Lévy .

Editor information

Editors and Affiliations

  1. Inserm GMGF UMR_S 910, Génomique Fonctionnelle INSERM UMR_S 910, Aix Marseille Université, Génétique Médicale, Marseille, France

    Pierre L. Roubertoux

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Lévy, N., Roubertoux, P.L. (2015). Organism Models: Choosing the Right Model. In: Roubertoux, P. (eds) Organism Models of Autism Spectrum Disorders. Neuromethods, vol 100. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2250-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2250-5_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2249-9

  • Online ISBN: 978-1-4939-2250-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation