biostudies-literatureJahic AGerman HSP patient organisationEuropean UnionIZKF JenaIZKF TübingenInvestissements d’avenirGerman Society of Clinical ChemistryGentechnologiestiftungFondation Roger de Spoelberch147https://www.ebi.ac.uk/biostudies/studies/S-EPMC4647479biostudies-literatureUnknown10<h4>Background</h4>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.<h4>Methods</h4>We generated a deletion-based knockout allele for E430025E21Rik, i.e. the murine homologue of KIAAOrphanet journal of rare diseasesThe spectrum of KIAA0196 variants, and characterization of a murine knockout: implications for the mutational mechanism in hereditary spastic paraplegia type SPG8.PMC4647479R12123DDNA2014ANR-10-IAIHU-06RS20121970-0-0FP7-E112009DD, FP7-E04006DD, FP7-2012-305121, PIOF-GA-2012-326681, and 01GM1408Bn.a.Jaenisch NKhundadze MBrice AKlebe SStevanin GSchule RJahic ABeetz CKassubek JKlimpe SFrahm CSchols LHubner CAfalseThe spectrum of KIAA0196 variants, and characterization of a murine knockout: implications for the mutational mechanism in hereditary spastic paraplegia type SPG8.<h4>Background</h4>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.<h4>Methods</h4>We generated a deletion-based knockout allele for E430025E21Rik, i.e. the murine homologue of KIAA2015-01-01T00:00:00Z2015 Nov2026-06-10T06:30:29.255Z2019-03-27T02:02:04ZS-EPMC46474792657274410.1186/s13023-015-0359-x