MafB is essential for renal development and F4/80 expression in macrophages

Takashi Moriguchi, Michito Hamada, Naoki Morito, Tsumoru Terunuma, Kazuteru Hasegawa, Chuan Zhang, Tomomasa Yokomizo, Ritsuko Esaki, Etsushi Kuroda, Keigyou Yoh, Takashi Kudo, Michio Nagata, David R. Greaves, James Douglas Engel, Masayuki Yamamoto, Satoru Takahashi

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)

Abstract

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-1-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-1-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.

Original languageEnglish
Pages (from-to)5715-5727
Number of pages13
JournalMolecular and cellular biology
Volume26
Issue number15
DOIs
Publication statusPublished - 2006 Aug

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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