Estrogen receptor-related receptors (ERRs) are orphan members of the nuclear receptor superfamily, closely related to the estrogen receptor. With a PCR-based cloning strategy we have identified two cDNA isoforms from a neonatal mouse whole brain cDNA library encoding ERRgamma. We show that alternative splicing gives rise to different 5'-ends. The predicted peptide sequence of ERRgamma2 differs from ERRgamma1 by additional 23 N-terminal residues. The presence of identical isoforms in human suggests a pivotal function of ERRgamma in mammalia. Northern blot analysis reveals that ERRgamma is expressed as early as day 11 of embryonic development (E11). Whole mount in situ hybridization analysis shows major expression of ERRgamma in the central nervous system at E12.5. In the adult mouse a 5.7 kb transcript is detected in heart, brain, kidney, and skeletal muscle. Therefore, ERRgamma may be involved in the differentiation, as well as the maintenance of the differentiated properties in the brain.
