Estrogen receptor-related receptors (ERRs) are orphan members of the nuclea
r receptor superfamily, closely related to the estrogen receptor. With a PC
R-based cloning strategy we have identified two cDNA isoforms from a neonat
al mouse whole brain cDNA library encoding ERR gamma. We show that alternat
ive splicing gives rise to different 5'-ends. The predicted peptide sequenc
e of ERR gamma 2 differs from ERR gamma 1 by additional 23 N-terminal resid
ues. The presence of identical isoforms in human suggests a pivotal functio
n of ERR gamma in mammalia. Northern blot analysis reveals that ERR gamma i
s expressed as early as day 11 of embryonic development (E11). Whole mount
in situ hybridization analysis shows major expression of ERR gamma in the c
entral nervous system at E12.5. in the adult mouse a 5.7 kb transcript is d
etected in heart, brain, kidney, and skeletal muscle. Therefore, ERR gamma
may be involved in the differentiation, as well as the maintenance of the d
ifferentiated properties in the brain. (C) 2000 Academic Press.