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Small Maf deficiency recapitulates the liver phenotypes of Nrf1‐ and Nrf2‐deficient mice
Author(s) -
Katsuoka Fumiki,
Yamazaki Hiromi,
Yamamoto Masayuki
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12445
Subject(s) - nrf1 , biology , phenotype , transcription factor , steatosis , knockout mouse , gene , microbiology and biotechnology , endocrinology , genetics
Nrf1 and Nrf2 ( NF ‐E2‐related factors 1 and 2, respectively) are transcription factors that belong to the Cap'n'collar ( CNC ) family and play critical roles in various tissues, including the liver. Liver‐specific Nrf1 knockout mice show hepatic steatosis, accompanied by dysregulation of various metabolic genes. Nrf2 knockout mice show impairment in the induction of antioxidant and xenobiotic‐metabolizing enzyme genes. Although it has been shown that small Maf ( sM af) proteins act as obligatory partners of CNC proteins, their precise contributions to the function of CNC proteins remain unclear especially in the context of adult liver functions. To address this issue, we generated mice that conditionally lack expression of all sM af proteins in the liver. The liver‐specific sM af‐deficient mice develop hepatic steatosis and dysregulation of genes involved in lipid and amino acid metabolism and proteasomal subunit expression. Importantly, the gene expression profiles in the sM af‐deficient livers share a strong similarity with those in Nrf1‐deficient livers. In addition, the basal expression levels of a number of Nrf2 target genes were diminished in the sM af‐deficient livers. These results provide the first genetic evidence that sM af proteins are indispensable for liver functions as heterodimeric partners for Nrf1 and Nrf2.