Horev, G., Ellegood, J., Lerch, J. P., Son, Y. E., Muthuswamy, L., Vogel, H., Krieger, A. M., Buja, A., Henkelman, R. M., Wigler, M. H., Mills, A. A. (October 2011) Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. Proceedings of the National Academy of Sciences of the United States of America, 108 (41). pp. 17076-81. ISSN 0027-8424
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Abstract
Recurrent copy number variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a "behavior trap" phenotype-a specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. These findings indicate that 16p11.2 CNVs cause brain and behavioral anomalies, providing insight into human neurodevelopmental disorders.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > congenital hereditary genetic diseases diseases & disorders > mental disorders > personality disorders > autism bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomal deletions organism description > animal > mammal > primates > hominids > human organism description > animal > mammal > rodent > mouse |
| CSHL Authors: | |
| Communities: | CSHL Post Doctoral Fellows CSHL labs > Mills lab CSHL labs > Wigler lab Stanley Institute for Cognitive Genomics |
| Depositing User: | CSHL Librarian |
| Date: | 3 October 2011 |
| Date Deposited: | 26 Oct 2011 20:33 |
| Last Modified: | 02 Jan 2018 21:52 |
| PMCID: | PMC3193230 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15648 |
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