Neonatal mortality and leanness in mice lacking the ARID transcription factor Mrf-2.
Proteins containing the ARID (AT-rich interaction domain) DNA-binding motif regulate gene expression and differentiation in fungi, plants, and animals. This report describes phenotypes resulting from targeted disruption of the ARID gene Mrf-2. Homozygous loss of Mrf-2 resulted in a high rate of neonatal mortality that was partially strain-dependent: survival of Mrf-2(-/-) pups ranged from 6.4% on the 129S1 genetic background to 38% on a mixed 129S1.C57Bl/6J background. Loss of Mrf-2 expression did not affect embryonic survival, embryonic growth or birth weight. Lipid accumulation was severely reduced in brown adipose of Mrf-2(-/-) neonates at 24h of age, however, and Mrf-2(-/-) mice weighed significantly less than controls from postnatal day five onward. Adult Mrf-2(-/-) mice were lean, with significant reductions in brown and white adipose tissues, and in the percentage of body fat. Mrf-2(-/-) and Mrf-2(+/-) mice were also resistant to weight gains and obesity when maintained on high-fat diets. These phenotypes suggest that Mrf-2 is essential for accumulation of lipid stores in postnatal life.
Whitson
Robert H
RH
Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, Duarte, CA 91010, USA. rwhitson@coh.org
Tsark
Walter
W
Huang
Ting H
TH
Itakura
Keiichi
K
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001824:Body Constitution / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D010641:Phenotype; D012737:Sex Factors; D013329:Structure-Activity Relationship; D015996:Survival Rate; D013851:Thinness / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
C503806:Arid5b protein, mouse; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors