title: MafB is essential for renal development and F4/80 expression in macrophages.
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.
authors.affiliation: Institute of Basic Medical Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Moriguchi
authors.forename: Michito
authors.initials: M
authors.lastname: Hamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Morito
authors.forename: Tsumoru
authors.initials: T
authors.lastname: Terunuma
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhang
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Esaki
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Keigyou
authors.initials: K
authors.lastname: Yoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D016177:Macrophage-1 Antigen; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D011993:Recombinant Fusion Proteins; C036763:monocyte-macrophage differentiation antigen