| 研究実績の概要 |
The project aimed to identify the vitamin A downstream targets that lead to induction of spermatogonial differentiation. In FY2019, we identified two vitamin A targets; MafB and c-Maf. We then generated the floxed alleles of each gene independently and then lines were mated to obtain double conditional knockout (KO) mice, in which Cre recombinase was activated upon tamoxifen treatment. We induced Cre activation at 6 weeks old mice and mice tissues were collected and the deletion of both genes were confirmed. In FY2020, we performed histological analyses of testis and other organs from the each single KO mice, and found that MafB and c-Maf expression pattern were changed in both KO mice, indicating that there exist an interaction between the gene expressions. In FY2021, MAFs KO lines identified podocyte as another candidate of MAFs function. Two weeks after Cre activation, the three generated lines developed overt proteinuria, thereby indicate that MafB and c-Maf plays an important role in podocytes. Their kidneys had a pale appearance and renal histopathological analysis of kidneys exhibit focal glomerular segmental sclerosis 16 weeks after tamoxifen administration. Glomerular sclerosis which can be rescued by retinoic acid agonist atRA failed to inhibit FSGS in MafB cKO mice, indicating that retinoic acid might prevent FSGS by induction of MAF proteins in glomeruli.
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