The spectrum of KIAA0196 variants, and characterization of a murine knockout: implications for the mutational mechanism in hereditary spastic paraplegia type SPG8.

ABSTRACT:

Background

The hereditary spastic paraplegias (HSPs) are rare neurodegenerative gait disorders which are genetically highly heterogeneous. For each single form, eventual consideration of therapeutic strategies requires an understanding of the mechanism by which mutations confer pathogenicity. SPG8 is a dominantly inherited HSP, and associated with rather early onset and rapid progression. A total of nine mutations in KIAA0196, which encodes the WASH regulatory complex (SHRC) member strumpellin, have been reported in SPG8 patients so far. Based on biochemical and cell biological approaches, they have been suggested to act via loss of function-mediated haploinsufficiency.

Methods

We generated a deletion-based knockout allele for E430025E21Rik, i.e. the murine homologue of KIAA

SUBMITTER: Jahic A 

PROVIDER: S-EPMC4647479 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature