Knockout neuronal microtubule motor protein Kif1b gene producing axonal neuron degeneration

Objective To investigate the pathology of heterozygous kif1b gene knockout mice as an animal model of Charcot-Marie-Tooth(CMT) disease. Methods Checking homologous recombination and genotype by southern blotting and PCR,surveying pathological changes in HE staining of spinal anterior horn,in CBB staining of sciatic nerve and in electron microscope. Results Southern blotting results showed homologous recombination happened in all of the 19 heterozygous kif1b knockout mice checked by PCR. Heterozygous Kif1b knockout mice showed axonal neuron degeneration and number decreasing in large diameter axons. Obstructed cellular organelles were found in local axon enlargement under light microscopy and electron microscopy,no change was found in myelinated fibers,segmental demyelation and onion bulb formation were not found. Typical acidophily sphenoid bodies were found in anterior horn cell bodies. Various cellular organelles clogged around nuclear and in axon entering region,including mussy neurofilament,mitochondria,vacuole and multi-vescular body. Neuronal numbers of spinal anterior horn decreased significantly. Conclusion The heterozygous Kif1b knockout mice mimic the pathological changes of human CMT disease. It is feasible to use those mice as animal model of CMT disease.