Role of prosaposin in the male reproductive system: Effect of prosaposin inactivation on the testis, epididymis, prostate, and seminal vesicles

SGP-1/prosaposin can be secreted or targeted to the lysosomes where it is p rocessed into smaller saposins (A, B, C, and D) required for the hydrolysis of glycosphingolipids. The deficiency of saposins B and C results in varia nt forms of metachromatic leukodystrophy and Gaucher's disease, respectivel y, which are characterized by lysosomal storage of undegraded glycosphingol ipids. Tn the nervous system, prosaposin presents trophic activity. A mouse model was recently developed by creating a null allele in embryonic stem c ells through gene targeting to investigate the phenotypic diversity of pros aposin mutations and the involvement of this protein in lysosomal storage d iseases, and for the development of therapeutic approaches. Mice homozygous mutants die at the age of 35-40 days and neurological disorders contribute to the early demise of the mutant mice. The male reproductive organs in ho mozygous mutants show several abnormalities, such as a decrease in testis s ize with reduced spermiogenesis and an involution of the prostate, seminal vesicles, and epididymis. In these animals, the blood levels of testosteron e remain normal. In the prostate of homozygous mutants, only the basal epit helial cells appear to be present, while the secretory cells are absent. Th ese findings suggest that prosaposin may be involved in the development and maintenance of the male reproductive organs, as well as, in cellular diffe rentiation.