Mice homozygous for the autosomal recessive mutation claw paw (clp) are characterized by limb posture abnormalities and congenital hypomyelination, with delayed onset of myelination of the peripheral nervous system but not the central nervous system. Although this combination of limb and peripheral nerve abnormalities in clp/clp mice might suggest a common neurogenic origin of the syndrome, it is not clear whether the clp gene acts primarily in the neurone, the Schwann cell or both. In the work described here, we address this question of cell autonomy of the clp mutation through reciprocal nerve grafting experiments between wild-type and clp/clp animals. Our results demonstrate that the clp mutation affects the Schwann cell compartment and possibly also the neuronal compartment. These data suggest that the clp gene product is expressed in Schwann cells as well as neurones and is likely to be involved in direct axon--Schwann cell interactions. Within the Schwann cell, clp affects a myelin-related signaling pathway that regulates periaxin and Krox-20 expression, but not Oct-6.

*Mutation, Animals, Axons/metabolism, DNA-Binding Proteins/genetics/metabolism, Early Growth Response Protein 2, Gene Expression Regulation, Developmental, Hoof and Claw/abnormalities, Membrane Proteins/genetics/metabolism, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Myelin Sheath/metabolism, Nerve Regeneration/genetics, Neural Conduction/genetics, Organic Cation Transport Proteins/genetics/metabolism, Schwann Cells/metabolism/*pathology, Sciatic Nerve/injuries/pathology/physiology/transplantation, Signal Transduction, Transcription Factors/genetics/metabolism, Transplants
dx.doi.org/10.1016/j.ydbio.2004.05.017, hdl.handle.net/1765/2659
Developmental Biology
Erasmus MC: University Medical Center Rotterdam

Darbas, A, Jaegle, M.M, Walbeehm, E.T, van der Burg, J, Broos, L.A.M, Uyl, M, … Driegen, M.J.F. (2004). Cell autonomy of the mouse claw paw mutation. Developmental Biology, 272(2), 470–482. doi:10.1016/j.ydbio.2004.05.017