S113R mutation in SLC33A1 leads to neurodegeneration and augmented BMP signaling in a mouse model.

ABSTRACT: The S113R mutation (c.339T>G) (MIM #603690.0001) in SLC33A1 (MIM #603690), an ER membrane acetyl-CoA transporter, has been previously identified in individuals with hereditary spastic paraplegia type 42 (SPG42; MIM #612539). SLC33A1 has also been shown to inhibit the bone morphogenetic protein (BMP) signaling pathway in zebrafish. To better understand the function of SLC33A1, we generated and characterized Slc33a1^S113R knock-in mice. Homozygous Slc33a1^S113R mutant mice were embryonic lethal, whereas heterozygous Slc33a1 mutant mice (Slc33a1^wt/mut) exhibited behavioral abnormalities and central neurodegeneration, which is consistent with hereditary spastic paraplegia (HSP) phenotypes. Importantly, we found an upregulation of BMP signaling in the nervous syst

SUBMITTER: Liu P 

PROVIDER: S-EPMC5278525 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature