Though much is known about the cytological and biochemical events of spermatogenesis, relatively little is known about controls over progression of cells through events of spermatogenic differentiation. Male sterile mouse mutants, blocked at various stages of spermatogenesis, are models for studying problems of regulation of spermatogenic differentiation not easily approached by other lines of investigation. Two critical control points during sperm development will be analyzed in the course of the proposed work. First, synthesis and assembly of sperm organelles will be studied using mice bearing autosomal mutations affecting sperm organelles. The accumulation and glycosylation of acrosomal enzymes will be investigated in mice homozygous for blind-sterile, a mutation affecting acrosome assembly, to determine if absence of these proteins causes the failure of acrosome assembly. To probe control of assembly and maintenance of the sperm tail, cellular distribution of tubulin and synthesis of testis-specific tubulin mRNA will be determined in mice homozygous for hop sterile, a mutation affecting sperm tail development. These studies will provide information about sequence and regulation of events involved in important aspects of spermiogenic differentiation. Second, the role of the sex chromosomes in regulating the progress of spermatocytes through meiosis will be studied in sterile male bearing X-autosome chromosome translocations and in sterile XO, sex-reversed males. These animals provide models to investigate the functional roles of the X and Y chromosomes in meiosis and also of the Y chromosome in spermiogenesis. Techniques of synaptonemal complex analysis after microspreading of spermatocyte chromosomes and autoradiography to monitor incorporation of 3H-uridine will be used to assess structural and functional states of the sex chromosomes in these sterile mice. The use of XO, sex-reversed males in this study will lead to information, heretofore unavailable, about the role of the Y chromosome in mammalian spermatogenesis. These experiments will also provide a critical test of the Lifschytz-Lindsley hypothesis of X-chromosome inactivation as an essential correlate of spermatogenesis.
| Handel, M A; Hunt, P A; Kot, M C et al. (1991) Role of sex chromosomes in the control of male germ-cell differentiation. Ann N Y Acad Sci 637:64-73 |
| Kot, M C; Handel, M A (1990) Spermatogenesis in XO,Sxr mice: role of the Y chromosome. J Exp Zool 256:92-105 |
| Handel, M A; Lane, P W; Schroeder, A C et al. (1988) New mutation causing sterility in the mouse. Gamete Res 21:409-23 |
| Kot, M C; Handel, M A (1987) Binding of morphologically abnormal sperm to mouse egg zonae pellucidae in vitro. Gamete Res 18:57-66 |
| Handel, M A (1987) Genetic control of spermatogenesis in mice. Results Probl Cell Differ 15:1-62 |
| Handel, M A; Washburn, L L; Rosenberg, M P et al. (1987) Male sterility caused by p6H and qk mutations is not corrected in chimeric mice. J Exp Zool 243:81-92 |
| Sotomayor, R E; Handel, M A (1986) Failure of acrosome assembly in a male sterile mouse mutant. Biol Reprod 34:171-82 |
