The testatin gene was previously isolated in a screen focused on finding novel signaling molecules involved in sex determination and differentiation. testatin is specifically upregulated in pre-Sertoli cells in early fetal development, immediately after the onset of Sry expression, and was therefore considered a strong candidate for involvement in early testis development. testatin expression is maintained in the adult Sertoli cell, and it can also be found in a small population of germ cells. Testatin shows homology to family 2 cystatins, a group of broadly expressed small secretory proteins that are inhibitors of cysteine proteases in vitro but whose in vivo functions are unclear. testatin belongs to a novel subfamily among the cystatins, comprising genes that all show expression patterns that are strikingly restricted to reproductive tissue. To investigate a possible role of testatin in testis development and male reproduction, we have generated a mouse with targeted disruption of the testatin gene. We found no abnormalities in the testatin knockout mice with regard to fetal and adult testis morphology, cellular ultrastructure, body and testis weight, number of offspring, spermatogenesis, or hormonal parameters (testosterone, luteinizing hormone, and follicle-stimulating hormone).The testis and the ovary arise from a common bipotential gonad during mammalian embryogenesis. During fetal life, at 11 days postcoitum (dpc) in the mouse, the indifferent gonad develops as a narrow band of tissue close to the kidney. The testis-determining gene Sry, located on the Y chromosome, acts dominantly to trigger differentiation of testes from the indifferent gonads that would otherwise develop as ovaries (22,29,48). Once the gonads begin to differentiate as testes, they secrete factors, notably anti-Müllerian hormone and testosterone, which determine further sexual development and are required for normal reproductive function in the adult individual. Disturbances in the initial sex-determining switch or in the subsequent differentiation of the testis will lead to incomplete sexual development in XY individuals who would otherwise develop as males.In addition to the master switch in sex determination, Sry, several genes have been identified that are involved in the formation of the indifferent gonad or subsequent differentiation of the testis. These include genes encoding, e.g., the transcription factors Sf1, Wt1, Emx1, Lhx9, M33, and Dmrt1 and the signaling molecules Fgf9, Wnt7a, Wnt4, and Dhh (reviewed in references 7 and 50). Despite the characterization of these genes, it is clear that key factors in gonad and testis development are lacking, and no genes that are directly regulated by the transcription factor Sry have been characterized.
