MafB is essential for renal development and F4/80 expression in macrophages
MafB is essential for renal development and F4/80 expression in macrophages
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DOI：
10.1128/mcb.00001-06
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发表时间：
2006-08-01
影响因子：
5.3
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Moriguchi, Takashi;Hamada, Michito;Takahashi, Satoru
mab是Maf转录因子家族的一员，它们具有相似的基本区域/亮氨酸拉链DNA结合基序和n端激活域。虽然众所周知，MafB在肾小球上皮细胞（足细胞）和巨噬细胞中特异性表达，但在这些组织中零突变表型的表征此前尚未报道。为了研究肾脏和巨噬细胞中可疑的MafB功能，我们制造了MafB /绿色荧光蛋白（GFP）敲入零突变小鼠。mab纯合突变体表现为肾发育不良，足细胞分化异常，肾小管凋亡。有趣的是，这些肾脏表型与几种肾脏疾病相关基因的表达减少有关。在造血细胞中，胎儿肝脏中表达Mac-1-和f4 /80的巨噬细胞均可见GFP荧光。有趣的是，在纯合子突变体中，巨噬细胞中F4/80的表达被抑制，尽管mac -l阳性巨噬细胞群体的发育不受影响。在原代培养的胎儿肝造血细胞中，发现MafB缺乏显著抑制非粘附巨噬细胞中F4/80的表达，而mac -l阳性巨噬细胞群体发育正常。这些结果表明，在不同的非贴壁成熟巨噬细胞亚群中，MafB对足细胞分化、肾小管存活和F4/80成熟至关重要。
MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains. Although it is well known that MafB is specifically expressed in glomerular epithelial cells (podocytes) and macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions in the kidney and in macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. mafB homozygous mutants displayed renal dysgenesis with abnormal podocyte differentiation as well as tubular apoptosis. Interestingly, these kidney phenotypes were associated with diminished expression of several kidney disease-related genes. In hematopoietic cells, GFP fluorescence was observed in both Mac-1- and F4/80-expressing macrophages in the fetal liver. Interestingly, F4/80 expression in macrophages was suppressed in the homozygous mutant, although development of the Mac-l-positive macrophage population was unaffected. In primary cultures of fetal liver hematopoietic cells, MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages, whereas the Mac-l-positive macrophage population developed normally. These results demonstrate that MafB is essential for podocyte differentiation, renal tubule survival, and F4/80 maturation in a distinct subpopulation of nonadherent mature macrophages.