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 24 h 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.