Apr 30, 2020

A mouse model for spinal muscular atrophy provides insights into non-alcoholic fatty liver disease pathogenesis

BioRxiv : the Preprint Server for Biology
M.-O. DeguiseRashmi Kothary


Background & aims Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and death in children. SMA patients are more susceptible to dyslipidemia as well as liver steatosis, features reproduced in SMA mouse models. As current pre-clinical models of NAFLD are invariably imperfect and generally take a long time to develop, the rapid development of liver steatosis in SMA mice provides a means to identify molecular markers of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Smn2B/- mice, a model of severe SMA, display typical features of NAFLD/non-alcoholic steatohepatitis (NASH). Methods Biochemical, histological, electron microscopy, proteomic, and high-resolution respirometry were used. Results The Smn2B/- mice mice develop steatohepatitis early in life. The consequent liver damage arises from mitochondrial reactive oxygen species production and results in impaired hepatic function including alterations in protein output, complement, coagulation, iron homeostasis, and IGF-1 metabolism. The steatohepatitis is reversible by AAV9-SMN gene therapy. The NAFLD phenotype is likely due to non-esterified fatty acid (NEFA) overload from peripheral lipolysis, subsequent to hyperglu...Continue Reading

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Mentioned in this Paper

Salmo salar
Untranslated Regions
RNA library
Regulation of Biological Process
Sequence Determinations, RNA
Transcription, Genetic

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