MafB is essential for renal development and F4/80 expression in macrophages.
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.
Moriguchi
Takashi
T
Institute of Basic Medical Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8575, Japan.
Hamada
Michito
M
Morito
Naoki
N
Terunuma
Tsumoru
T
Hasegawa
Kazuteru
K
Zhang
Chuan
C
Yokomizo
Tomomasa
T
Esaki
Ritsuko
R
Kuroda
Etsushi
E
Yoh
Keigyou
K
Kudo
Takashi
T
Nagata
Michio
M
Greaves
David R
DR
Engel
James Douglas
JD
Yamamoto
Masayuki
M
Takahashi
Satoru
S
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
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