Rev-erbAα-/- mice have a β-geo cassette replacing part of exon 2, all of exons 3-5, and part of exon 6 of the nuclear receptor subfamily 1, group D, member 1 (Nr1d1) gene, abolishing gene function. Rev-erbAα is a nuclear receptor and transcriptional
repressor that regulates circadian clock function, metabolism, and postnatal cerebellar development. Homozygous males are viable and exhibit reduced fertility. Homozygous females have reduced fertility with only 32% producing litters. These mice develop normally until 2 weeks of age, when they exhibit delayed cerebellum development including abnormal Purkinje cells and granule cells, and increased apoptosis of neurons in the internal granule cell layer. Rev-erbAα deletion in these mice also disturbs the circadian rhythm in the liver leading to increased hepatic lipogenesis and a 2-fold increase in hepatic triglyceride content. This liver steatosis is similar to that seen in people who suffer from obesity, diabetes, and metabolic syndrome due to misalignment of fasting/feeding and sleep/wake cycles. lacZ expression is evident during embryogenesis in the heart starting at 10.5 days postcoitus
and 1 day later in the developing eye. In the adult expression is seen in many cell types, including brain, liver, skeletal myotubes, cardiocytes, as well as in the smooth muscle layers surrounding the intestine and the uterus.
