Abstract
The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax -/- mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax -/- mice to generate the experimental mouse line (Bax -/-, 9-2 +/+). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax -/- mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.
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