Archival ReportA Mouse Model that Recapitulates Cardinal Features of the 15q13.3 Microdeletion Syndrome Including Schizophrenia- and Epilepsy-Related Alterations
Section snippets
Human Subjects
Four male and 11 female subjects (mean age 54 ± 16.0 years) were identified using deCODE’s database of 95,085 genotyped Icelandic individuals after excluding psychiatric phenotypes (autism, schizophrenia, and bipolar disorder) and individuals receiving antipsychotic drugs. Control subjects (40 male subjects, 110 female subjects) were matched for year of birth and sex from the database. All subjects provided written, informed consent for participation, and approval was obtained from the National
Basic Behavior and Physiology Is Normal in Df(h15q13)/+ Mice
A mouse model of the human 15q13.3 deletion syndrome was generated by deletion of the orthologous genomic region on mouse chromosome 7. Animals were born at expected ratios (hemizygous fraction .52, 95% confidence interval: .39 to .64), but survival of Df(h15q13)/+ pups at weaning was slightly reduced with a hemizygous fraction of .45 (95% confidence interval: .42 to .47, n = 488/1084). For further characterization, hemizygous male mice were compared with wild-type littermates.
Overall,
Discussion
We have generated a mouse model of the human 15q13.3 microdeletion syndrome that recapitulates some physiological and behavioral characteristics of the human carriers. We have focused on schizophrenia and epilepsy aspects (Table S2 in Supplement 1) due to the strong association with these disorders, but we serendipitously discovered aggression and weight phenotypes that are also present in human microdeletion carriers. Several groups have reported aggressive behavior in carriers of the 15q13.3
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Authors KF and JN contributed equally to this work.