Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder.
作者： Claudia Fuchs , Laura Gennaccaro , Stefania Trazzi , Stefano Bastianini , Simone Bettini
DOI: 10.1155/2018/9726950
关键词:
摘要: CDKL5 disorder is a severe neurodevelopmental caused by mutations in the X-linked (cyclin-dependent kinase-like five) gene. primarily affects girls and characterized early-onset epileptic seizures, gross motor impairment, intellectual disability, autistic features. Although all female patients are heterozygous, most valid disease-related model, heterozygous Cdkl5 knockout (Cdkl5 +/-) mouse, has been little characterized. The lack of detailed behavioral profiling this model remains crucial gap that must be addressed order to advance preclinical studies. Here, we provide molecular characterization +/- mice. We found mice reliably recapitulate several aspects disorder, including autistic-like behaviors, defects coordination memory performance, breathing abnormalities. These associated with neuroanatomical alterations, such as reduced dendritic arborization spine density hippocampal neurons. Interestingly, show age-related alterations protein kinase B (AKT) extracellular signal-regulated (ERK) signaling, two signaling pathways involved many processes. In conclusion, our study provides comprehensive overview neurobehavioral phenotypes demonstrates might valuable animal studies on disorder.
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