دانلود مقاله ISI انگلیسی شماره 128338
کد مقاله سال انتشار مقاله انگلیسی ترجمه فارسی تعداد کلمات
128338 2018 13 صفحه PDF سفارش دهید 7783 کلمه
خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.
عنوان انگلیسی
Otud7a Knockout Mice Recapitulate Many Neurological Features of 15q13.3 Microdeletion Syndrome
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : The American Journal of Human Genetics, Volume 102, Issue 2, 1 February 2018, Pages 296-308

پیش نمایش مقاله
پیش نمایش مقاله

چکیده انگلیسی

15q13.3 microdeletion syndrome is characterized by a wide spectrum of neurodevelopmental disorders, including developmental delay, intellectual disability, epilepsy, language impairment, abnormal behaviors, neuropsychiatric disorders, and hypotonia. This syndrome is caused by a deletion on chromosome 15q, which typically encompasses six genes. Here, through studies on OTU deubiquitinase 7A (Otud7a) knockout mice, we identify OTUD7A as a critical gene responsible for many of the cardinal phenotypes associated with 15q13.3 microdeletion syndrome. Otud7a-null mice show reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalizations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle. We show that OTUD7A localizes to dendritic spines and that Otud7a-null mice have decreased dendritic spine density compared to their wild-type littermates. Furthermore, frequency of miniature excitatory postsynaptic currents (mEPSCs) is reduced in the frontal cortex of Otud7a-null mice, suggesting a role of Otud7a in regulation of dendritic spine density and glutamatergic synaptic transmission. Taken together, our results suggest decreased OTUD7A dosage as a major contributor to the neurodevelopmental phenotypes associated with 15q13.3 microdeletion syndrome, through the misregulation of dendritic spine density and activity.

خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.