nNeuronal specific dependence for an ubiquitous molecular motor.

CROMBERG L; FALZONE T

Huerta Grande, Cordoba

Congreso; XXIX congreso de la SAN; 2014

SAN

The molecular motor family kif5 transport cargoes, such as app, active zone vesicles, mitochondria, trKb and ion channels, in an anterograde way along the axon to the synapses. Many  studies have focus on the molecular properties of kif5b motor, however, its role in neuron function and physiology remains unclear. Because Kif5b knockout mice are lethal, we deleted kif5b from neurons using a conditional CRE strategy  to achieve a better comprehension of the relevance of kif5b in neuronal physiology. Mice with both kif5b alleles flanked by loxp sequences were crossed with knockin mice expressing CRE recombinase under the nestin promoter.  Surprisingly, kif5b conditional knockout mice were viable, showed similar brain volume and have no apparent phenotype. Interestingly, their locomotor response was impaired showing less covered distance and more pauses in an open field assay. To test for locomotors impairments associated with fine coordination we perform a rotarod test. During the first trials knockout mice showed higher number of fallings although they reach a normal performance at the last trial. To test whether locomotor coordination defects were induced by compromised nigrostriatal neurons due to deletions of kif5b we conditionally deleted kif5b from dopaminergic neurons. Contrary to what we expected, kif5b deletion in dopaminergic neurons did not impair locomotor ability neither in open field or rotarod assays. Taken together, these results suggest the presence of specific neuron dependence for kif5b and support the interesting possibility that  dopaminergic neuronal pathways are not affected by kif5b deletion.