Abstract

The formation of mature germ cells in the adult male animal is a unique developmental system. Spermatogenesis requires the maintenance of a stem cell pool which can self renew and can undergo a complicated differentiation process to form the haploid male gamete. The introduction of new genes into mice provides a powerful method by which to study this complicated process and may reveal novel mechanisms for gene regulation. We propose studies in four areas. 1. To identify the cis-acting regulatory elements required for spermatid specific transcription of the mouse protamine-1 gene, which codes for a unique protein involved in sperm chromatin condensation. 2. To determine the role of RNA sequences in the translational regulation and stability of protamine message. 3. To establish the degree of macromolecular movement between syncytial spermatids during differentiation. 4. To analyze two transgenic mouse lines which process distinct characteristic defects in male germ cell development. These experiments represent a new approach to the study of spermatogenesis and will provide insight into the process of differentiation and gene regulation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37HD023657-06
Application #
3485179
Study Section
Special Emphasis Panel (NSS)
Project Start
1988-02-01
Project End
1998-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Nagano, M; Brinster, R L (1998) Spermatogonial transplantation and reconstitution of donor cell spermatogenesis in recipient mice. APMIS 106:47-55;discussion 56-7
Quaife, C J; Kelly, E J; Masters, B A et al. (1998) Ectopic expression of metallothionein-III causes pancreatic acinar cell necrosis in transgenic mice. Toxicol Appl Pharmacol 148:148-57
Ogawa, T; Arechaga, J M; Avarbock, M R et al. (1997) Transplantation of testis germinal cells into mouse seminiferous tubules. Int J Dev Biol 41:111-22
Kelly, E J; Sandgren, E P; Brinster, R L et al. (1997) A pair of adjacent glucocorticoid response elements regulate expression of two mouse metallothionein genes. Proc Natl Acad Sci U S A 94:10045-50
Russell, L D; Franca, L R; Brinster, R L (1996) Ultrastructural observations of spermatogenesis in mice resulting from transplantation of mouse spermatogonia. J Androl 17:603-14
Russell, L D; Brinster, R L (1996) Ultrastructural observations of spermatogenesis following transplantation of rat testis cells into mouse seminiferous tubules. J Androl 17:615-27
Erickson, J C; Masters, B A; Kelly, E J et al. (1995) Expression of human metallothionein-III in transgenic mice. Neurochem Int 27:35-41
Rhim, J A; Connor, W; Dixon, G H et al. (1995) Expression of an avian protamine in transgenic mice disrupts chromatin structure in spermatozoa. Biol Reprod 52:20-32
Rhim, J A; Sandgren, E P; Palmiter, R D et al. (1995) Complete reconstitution of mouse liver with xenogeneic hepatocytes. Proc Natl Acad Sci U S A 92:4942-6
Masters, B A; Kelly, E J; Quaife, C J et al. (1994) Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium. Proc Natl Acad Sci U S A 91:584-8

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