Kayla R. Nygaard, Susan E. Maloney, Raylynn G. Swift, Katherine B. McCullough, Rachael E. Wagner, Stuart B. Fass, Krassimira Garbett, Karoly Mirnics, Jeremy Veenstra-VanderWeele, Joseph D. Dougherty
{"title":"Williams综合征小鼠模型的广泛表征显示gtf2ird1介导的选择性感觉运动任务的拯救,但对增强的社会行为没有影响","authors":"Kayla R. Nygaard, Susan E. Maloney, Raylynn G. Swift, Katherine B. McCullough, Rachael E. Wagner, Stuart B. Fass, Krassimira Garbett, Karoly Mirnics, Jeremy Veenstra-VanderWeele, Joseph D. Dougherty","doi":"10.1111/gbb.12853","DOIUrl":null,"url":null,"abstract":"<p>Williams syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety and specific phobias along with perturbed motor function. Williams syndrome is caused by a microdeletion of 26–28 genes on chromosome 7, including <i>GTF2IRD1</i>, which encodes a transcription factor suggested to play a role in the behavioral profile of Williams syndrome. Duplications of the full region also lead to frequent autism diagnosis, social phobias and language delay. Thus, genes in the region appear to regulate social motivation in a dose-sensitive manner. A “complete deletion” mouse, heterozygously eliminating the syntenic Williams syndrome region, has been deeply characterized for cardiac phenotypes, but direct measures of social motivation have not been assessed. Furthermore, the role of <i>Gtf2ird1</i> in these behaviors has not been addressed in a relevant genetic context. Here, we have generated a mouse overexpressing <i>Gtf2ird1</i>, which can be used both to model duplication of this gene alone and to rescue <i>Gtf2ird1</i> expression in the complete deletion mice. Using a comprehensive behavioral pipeline and direct measures of social motivation, we provide evidence that the Williams syndrome critical region regulates social motivation along with motor and anxiety phenotypes, but that <i>Gtf2ird1</i> complementation is not sufficient to rescue most of these traits, and duplication does not decrease social motivation. However, <i>Gtf2ird1</i> complementation does rescue light-aversive behavior and performance on select sensorimotor tasks, perhaps indicating a role for this gene in sensory processing or integration.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12853","citationCount":"0","resultStr":"{\"title\":\"Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior\",\"authors\":\"Kayla R. Nygaard, Susan E. Maloney, Raylynn G. Swift, Katherine B. McCullough, Rachael E. Wagner, Stuart B. Fass, Krassimira Garbett, Karoly Mirnics, Jeremy Veenstra-VanderWeele, Joseph D. Dougherty\",\"doi\":\"10.1111/gbb.12853\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Williams syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety and specific phobias along with perturbed motor function. Williams syndrome is caused by a microdeletion of 26–28 genes on chromosome 7, including <i>GTF2IRD1</i>, which encodes a transcription factor suggested to play a role in the behavioral profile of Williams syndrome. Duplications of the full region also lead to frequent autism diagnosis, social phobias and language delay. Thus, genes in the region appear to regulate social motivation in a dose-sensitive manner. A “complete deletion” mouse, heterozygously eliminating the syntenic Williams syndrome region, has been deeply characterized for cardiac phenotypes, but direct measures of social motivation have not been assessed. Furthermore, the role of <i>Gtf2ird1</i> in these behaviors has not been addressed in a relevant genetic context. Here, we have generated a mouse overexpressing <i>Gtf2ird1</i>, which can be used both to model duplication of this gene alone and to rescue <i>Gtf2ird1</i> expression in the complete deletion mice. Using a comprehensive behavioral pipeline and direct measures of social motivation, we provide evidence that the Williams syndrome critical region regulates social motivation along with motor and anxiety phenotypes, but that <i>Gtf2ird1</i> complementation is not sufficient to rescue most of these traits, and duplication does not decrease social motivation. 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Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior
Williams syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety and specific phobias along with perturbed motor function. Williams syndrome is caused by a microdeletion of 26–28 genes on chromosome 7, including GTF2IRD1, which encodes a transcription factor suggested to play a role in the behavioral profile of Williams syndrome. Duplications of the full region also lead to frequent autism diagnosis, social phobias and language delay. Thus, genes in the region appear to regulate social motivation in a dose-sensitive manner. A “complete deletion” mouse, heterozygously eliminating the syntenic Williams syndrome region, has been deeply characterized for cardiac phenotypes, but direct measures of social motivation have not been assessed. Furthermore, the role of Gtf2ird1 in these behaviors has not been addressed in a relevant genetic context. Here, we have generated a mouse overexpressing Gtf2ird1, which can be used both to model duplication of this gene alone and to rescue Gtf2ird1 expression in the complete deletion mice. Using a comprehensive behavioral pipeline and direct measures of social motivation, we provide evidence that the Williams syndrome critical region regulates social motivation along with motor and anxiety phenotypes, but that Gtf2ird1 complementation is not sufficient to rescue most of these traits, and duplication does not decrease social motivation. However, Gtf2ird1 complementation does rescue light-aversive behavior and performance on select sensorimotor tasks, perhaps indicating a role for this gene in sensory processing or integration.
期刊介绍:
Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes.
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