Molenhuis, RT;
Bruining, H;
Brandt, MJV;
Van Soldt, PE;
Atamni, HJA-T;
Burbach, JPH;
Iraqi, FA;
... Kas, MJH; + view all
(2018)
Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice.
Molecular Autism
, 9
, Article 63. 10.1186/s13229-018-0252-2.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13229-018-0252-2 |
| Publisher version: | https://doi.org/10.1186/s13229-018-0252-2 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Neurodevelopmental disorders, Autism, Animal models, Quantitative genetics, Genetic reference population, Behavioral neuroscience, Histamine 3 receptor, Repetitive behavior |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10064814 |
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