NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
Year: 2021
Type: article
Abstract: BACKGROUND: Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells. RESULTS: We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development. CONCLUSIONS: We reveal the abnormal regulation of these mRNAs in the Fmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.
Source: Genome biology
Authors: Tatsuaki Kurosaki, Hitomi Sakano, Christoph Pröschel, Jason Wheeler, Alexander Hewko, Lynne E. Maquat
Institutions: University of Rochester Medicine, University of Rochester
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,890
Funders: FRAXA Research Foundation, University of Rochester, National Institutes of Health, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research
Awards: G1500332416, G2482925359, G3785387297, G5520316217, G6078287459, iPSC-derived astrocytes to model Vanishing White Matter Disease, G8836271271, G9000103447, G9000238780, Role of Fragile X Mental Retardation Protein on Gene Expression in Auditory Brainstem Development, Rochester Resource-Based Center for Bone, Muscle and Orthopaedic Research (ROCSTARR) (Overall Application)
OpenAlex ID: W3211399722