Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

Abstract

By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice

Brain masculinization requires androgen receptor function

“…AR LϪ/Y mice exhibited femaletypical external appearance, including a vagina with a blind end, and a clitoral-like phallus instead of a penis and scrotum (Fig. 1g), similar to that observed in another mice line (18). Male reproductive organs, including seminal vesicles, vas deferens, epididymis, and prostate, were absent in AR LϪ/Y mice (Fig.…”

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

“…It is known that androgens and their cognate receptors are critical in determining the male phenotype and their roles in spermatogenesis have been widely investigated (Ghosh et al, 1991;O'shaughnessy et al, 2002;Yeh et al, 2002;Tsai et al, 2006;Wang et al, 2009). On the other hand, there is little information concerning the influence of androgen/AR signaling on germ cell differentiation during the fetal and neonatal periods.…”

Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells

“…1). The generation of floxed AR gene-targeted mice has been described (12,15). The expression of transgelin promoter-driven Cre recombinase can efficiently and selectively delete the floxed AR gene in PM cells.…”

“…The local actions of androgen on testis functions were initially demonstrated when testosterone alone, in the absence of the gonadotropins, leuteinizing hormone (LH), and follicle-stimulating hormone (FSH), could support spermatogenesis (11). Furthermore, AR has been detected in Sertoli, Leydig, PM, and spermatid cells (round and elongated) (2,3), and mice lacking functional AR develop testicular feminization syndrome (12). Previously, we have shown that Sertoli cellspecific AR Ϫ/y mice revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility (13).…”

“…Given the specific roles of PM cells in regulation of functional testes (14), we were interested in generating PM cell-specific AR knockout (PM-AR Ϫ/y ) mice by using the Tagln (transgelin, smooth muscle protein 22-␣)-Cre͞loxP system (12,(15)(16)(17). By mating floxed AR mice (12) with a transgenic line possessing Tagln promoter-driven expression of the Cre recombinase (17), we obtained male PM-AR Ϫ/y mice with the AR gene deleted in PM cells.…”