Down but not out? A novel protein isoform of the estrogen receptor α is expressed in the estrogen receptor α knockout mouse

Abstract

The mouse knockout of the estrogen receptor α (ERα) gene, known as αERKO, has been extensively used for several years to study the role and function of ERα. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ERα. Although alternatively spliced ERα mRNA variants in the αERKO mouse were reported previously, the corresponding protein isoforms have not been detected to date. Here we show that a variant ERα protein, 61 kDa in size, is expressed in the uterine tissue of αERKO mice as a result of an alternative splicing. The transactivation capability of this protein is cell dependent and can be as high as 75% of the wild type ERα.