Functional Study Of Cytoskeleton Protein Palladin And Kif18a In Mice

We use mouse model to study the role of actin cytoskeleton associated protein palladin and microtubule based kinesin member kif18a. We constructed palladin knockout mice, and found palladin disruption resulted in neural tube closure defects specifically in the cranial region, failure of ventral body wall closure and lethality before embryonic day 15.5. Palladin deficient embryonic heart shows apparent development defect and the Z-line of palladin deficient myocardium is attenuated and disorganized. Palladin deficient cardiocyte also has some functional defects. Studies conducted with palladin deficient mouse embryonic fibroblasts show that palladin regulates cell-extracellular matrix interaction through maintaining normal actin cytoskeleton architecture and stabilizingβ1-integrin. Palladin and Rho signal pathway are separate signals that regulate actin cytoskeleton dynamics. Loss of palladin expression causes a compensated up-regulation of Rho signal. Further study indicates palladin deficient mice exhibit defective definitive fetal liver erythropoiesis. Increased erythroblast apoptosis and partial differentiation blockage were observed after palladin disruption. The intrinsic defect of palladin deficient fetal liver macrophage in binding erythroblasts may be the major cause of defective definitive erythropoiesis after palladin disruption. Kif18a mutant mouse was obtained by chance through transgenic insertion mutation. In mouse genome, kif18a has many isoforms, and kif18a1 which contains exons from exon 1 to exon 17 is the mature testis specific isoform. Kif18a1 is specificly expressed in meiotic spindle and maturing spermatids. Kif18a mutation results in spermatogenetic defects in three levels: spermatogonia proliferation defect, meiotic spindle formation defect and maturing defects of spermatids. Kif18a mutant mouse is an excellent model for the study of mammalian spermatogenesis and the in vivo function of kinesin.