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

The mouse knockout of the estrogen receptor alpha (ER alpha) gene, known as alpha ERKO, has been extensively used for several years to study the role and function of ER alpha. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ER alpha. Although alternatively spliced ER alpha mRNA variants in the alpha ERKO mouse were reported previously, the corresponding protein isoforms have not been detected to date. Here we show that a variant ER alpha protein, 61 kDa in size, is expressed in the uterine tissue of alpha ERKO 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 ER alpha.