TARGETED DISRUPTION OF MOUSE CONVENTIONAL KINESIN HEAVY-CHAIN, KIF5B,RESULTS IN ABNORMAL PERINUCLEAR CLUSTERING OF MITOCHONDRIA

Mouse kif5B gene was disrupted by homologous recombination. kif5B(-/-) mice were embryonic lethal with a severe growth retardation at 9.5-11 .5 days postcoitum. To analyze the significance of this conventional k inesin heavy chain in organelle transport, we studied the distribution of major organelles in the extraembryonic cells. The null mutant cell s impaired lysosomal dispersion, while brefeldin A could normally indu ce the breakdown of their Golgi apparatus. More prominently, their mit ochondria abnormally clustered in the perinuclear region. This mitocho ndrial phenotype was reversed by an exogeneous expression of KIF5B, an d a subcellular fractionation revealed that KIF5B is associated with m itochondria. These data collectively indicate that kinesin is essentia l for mitochondrial and lysosomal dispersion rather than for the Golgi -to-ER traffic in these cells.