Generation of a new Cre-deleter mouse line to study spermiogenesis

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Project Summary The goal of this proposal is to generate and characterize a round spermatid-specific Cre deleter mouse line. Currently, there is no Cre-deleter mouse line available that targets deletion of a floxed gene specifically in round spermatids. The available testis germ cell Cre-lines delete floxed genes either in spermatogonia (Stra8- iCre) or in spermatocytes (Spo11-Cre, Hsp2a-Cre). These lines are not suitable for studying the biology of round spermatids because their use would cause a phenotype prior to the formation of haploid cells. We will generate a transgenic mouse line in which the well-characterized round spermatid-specific promoter of the mouse Acrv1 gene will drive the expression of Cre recombinase. Accomplishment of this project goal will provide a novel mouse line that will enable researchers to assess the function of ubiquitously expressed genes during round spermatid differentiation (spermiogenesis). Using this novel Cre-line (Acrv1-Cre), we propose to test the hypothesis that the ubiquitously expressed TAR DNA/RNA binding protein of 43 kilodaltons (TDP-43) is essential for spermiogenesis. Our previous work has established that TDP-43 is critical for male fertility. TDP-43 is expressed in the round spermatids as well as in the manchette of step 9-11 spermatids. The Acrv1-Cre mouse will allow us to test its role during spermiogenesis. Thus, the innovative part is that this proposal accomplishes two goals simultaneously. This proposal fulfils the stated purpose of the funding opportunity PA-20-200. It will develop new research technology (round spermatid-specific Cre deleter mouse line) and serve as a pilot and feasibility study to focus on the role of TDP-43 in spermiogenesis. It is a smallresearch project that can be carried out in a short period with limited resources.