Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice / R. T. MOLENHUIS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 63 p. Titre : Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice Type de document : Texte imprimé et/ou numérique Auteurs : R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; M. J. V. BRANDT, Auteur ; P. E. VAN SOLDT, Auteur ; H. J. ABU-TOAMIH ATAMNI, Auteur ; J. P. H. BURBACH, Auteur ; F. A. IRAQI, Auteur ; R. F. MOTT, Auteur ; M. J. H. KAS, Auteur Article en page(s) : 63 p. Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/*genetics  Genetics, Behavioral/*methods/standards  Genome-Wide Association Study/*methods/standards  Male  Mice  Mice, Inbred C57BL  Multifactorial Inheritance  Quantitative Trait Loci  Reference Standards  *Animal models  *Autism  *Behavioral neuroscience  *Genetic reference population  *Histamine 3 receptor  *Neurodevelopmental disorders  *Quantitative genetics  *Repetitive behavior  Care and Use Committee of Tel Aviv University.Not applicable.The authors declare  that they have no competing interests.Springer Nature remains neutral with regard  to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation on a fixed genetic background. Recent human genetic studies however indicate that a clinical diagnosis with ASDAutism Spectrum Disorder (ASD) is almost always associated with multiple genetic fore- and background changes. The translational value of animal model studies would be greatly enhanced if genetic insults could be studied in a more quantitative framework across genetic backgrounds. Methods: We used the Collaborative Cross (CC), a novel mouse genetic reference population, to investigate the quantitative genetic architecture of mouse behavioral phenotypes commonly used in animal models for NDD. Results: Classical tests of social recognition and grooming phenotypes appeared insufficient for quantitative studies due to genetic dilution and limited heritability. In contrast, digging, locomotor activity, and stereotyped exploratory patterns were characterized by continuous distribution across our CC sample and also mapped to quantitative trait loci containing genes associated with corresponding phenotypes in human populations. Conclusions: These findings show that the CC can move animal model studies beyond comparative single gene-single background designs, and point out which type of behavioral phenotypes are most suitable to quantify the effect of developmental etiologies across multiple genetic backgrounds. En ligne : https://dx.doi.org/10.1186/s13229-018-0252-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice [Texte imprimé et/ou numérique] / R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; M. J. V. BRANDT, Auteur ; P. E. VAN SOLDT, Auteur ; H. J. ABU-TOAMIH ATAMNI, Auteur ; J. P. H. BURBACH, Auteur ; F. A. IRAQI, Auteur ; R. F. MOTT, Auteur ; M. J. H. KAS, Auteur . - 63 p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 63 p. Mots-clés : Animals  Autism Spectrum Disorder/*genetics  Genetics, Behavioral/*methods/standards  Genome-Wide Association Study/*methods/standards  Male  Mice  Mice, Inbred C57BL  Multifactorial Inheritance  Quantitative Trait Loci  Reference Standards  *Animal models  *Autism  *Behavioral neuroscience  *Genetic reference population  *Histamine 3 receptor  *Neurodevelopmental disorders  *Quantitative genetics  *Repetitive behavior  Care and Use Committee of Tel Aviv University.Not applicable.The authors declare  that they have no competing interests.Springer Nature remains neutral with regard  to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation on a fixed genetic background. Recent human genetic studies however indicate that a clinical diagnosis with ASDAutism Spectrum Disorder (ASD) is almost always associated with multiple genetic fore- and background changes. The translational value of animal model studies would be greatly enhanced if genetic insults could be studied in a more quantitative framework across genetic backgrounds. Methods: We used the Collaborative Cross (CC), a novel mouse genetic reference population, to investigate the quantitative genetic architecture of mouse behavioral phenotypes commonly used in animal models for NDD. Results: Classical tests of social recognition and grooming phenotypes appeared insufficient for quantitative studies due to genetic dilution and limited heritability. In contrast, digging, locomotor activity, and stereotyped exploratory patterns were characterized by continuous distribution across our CC sample and also mapped to quantitative trait loci containing genes associated with corresponding phenotypes in human populations. Conclusions: These findings show that the CC can move animal model studies beyond comparative single gene-single background designs, and point out which type of behavioral phenotypes are most suitable to quantify the effect of developmental etiologies across multiple genetic backgrounds. En ligne : https://dx.doi.org/10.1186/s13229-018-0252-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

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