biostudies-literatureCollinson JMFundação para a Ciência e a TecnologiaMedical Research CouncilBritish Society for Developmental BiologyAnatomical Societydev160093https://www.ebi.ac.uk/biostudies/studies/S-EPMC5818009biostudies-literatureUnknown145(3)Genetic factors underlying the human limb abnormality congenital talipes equinovarus ('clubfoot') remain incompletely understood. The spontaneous autosomal recessive mouse 'peroneal muscular atrophy' mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent. In this study, the primary developmental defect was identified as a reduced growth of sciatic nerve lateral motor column (LMC) neurons leading to failure to project to dorsal (peroneal) lower limb muscle blocks. The <i>pma</i> mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (<i>Limk1</i>) identified, which is upregulated in mutant lateral LMC motor neurons. Genetic and molecular analyses showed that the mutation acts in the EphA4-Development (Cambridge, England)The developmental and genetic basis of 'clubfoot' in the peroneal muscular atrophy mutant mouse.PMC5818009G080090187379Lindstrom NOWallace KOras KRoss ZKVargesson NNakamoto MMbogo IDuce SMiedzybrodzka ZCollinson JMFraser AMNeves CMeharg CBarker SCharles RHfalseThe developmental and genetic basis of 'clubfoot' in the peroneal muscular atrophy mutant mouse.Genetic factors underlying the human limb abnormality congenital talipes equinovarus ('clubfoot') remain incompletely understood. The spontaneous autosomal recessive mouse 'peroneal muscular atrophy' mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent. In this study, the primary developmental defect was identified as a reduced growth of sciatic nerve lateral motor column (LMC) neurons leading to failure to project to dorsal (peroneal) lower limb muscle blocks. The <i>pma</i> mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (<i>Limk1</i>) identified, which is upregulated in mutant lateral LMC motor neurons. Genetic and molecular analyses showed that the mutation acts in the EphA4-2018-01-01T00:00:00Z2018 Feb2026-06-07T06:44:32.169Z2019-03-26T23:48:51ZS-EPMC58180092943913310.1242/dev.160093