Mrf-2 is essential for accumulation of lipid stores in postnatal life. Homozygous loss of the ARID gene Mrf-2 resulted in a high rate of neonatal mortality that was partially strain-dependent in mice. 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 hours 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.