BRCA1 and breast cancer: Furthermore, it has been demonstrated in mouse models of familial breast cancer that the I26A mutation in the RING domain of BRCA1 that does not disrupt its heterodimerization with BARD1, but abolishes its E3 ligase activity firstly does not cause embryonic lethality and animals grow to normal adulthood, although male animals are sterile; and secondly the rate of spontaneous tumor formation is the same as in animals expressing wild type BRCA1 thus suggesting that it is not the E3 ligase activity of BRCA1 that confers its tumor suppression function [69].