Medicine and Health Sciences Commons^™

The Developmental And Genetic Basis Of ‘Clubfoot’ In The Peroneal Muscular Atrophy Mutant Mouse, J. Martin Collinson, Nils Lindström, Carlos Neves, Karen Wallace, Caroline Meharg, Rebecca Charles, Zoe Ross, Amy Fraser, Ivan Mbogo, Kadri Oras, Masaru Nakamoto, Simon Barker, Suzanne Duce, Zosia Miedzybrodzka, Neil Vargesson

Biology Faculty Publications

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 pma mutation was mapped and a candidate gene encoding LIM-domain kinase 1 (Limk1) identified, which is upregulated in mutant lateral LMC …