LOCOMOTION CHARACTERIZATION OF DCC AND NCK2 MUTANT MICE

Abstract

ABSTRACT Transmembrane receptor protein DCC (deleted in colorectal cancer) and its intracellular binding partner Nck (non-catalytic tyrosine kinase adaptor protein) are both important in spinal locomotor network formation. Depletion of DCC or both Nck proteins cause altered left-right coordination. The distinct function of Nck1 and Nck2 and their relation to DCC in locomotion is unclear. A novel genetic mutation method enabled us to study the locomotion in adult DCC deficient and Nck2 knockout mice. DCC deficiency in the spinal cord causes hindlimb synchronization, and a decrease in locomotion speed caused by decreased stride length, which is partially compensated by increased stride frequency. Nck2 depletion causes elongated swing duration and increased ankle flexor and extensor 1 phase, accompanied by in phase elongation of flexor muscle activation and more abrupt extensor muscle activation. The distinct phenotypes of the mutant animals indicate Nck2’s distinct role in locomotion through partially DCC-independent pathway.