title: The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.
abstract: The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.
authors.affiliation: The Lerner Research Institute, Department of Molecular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Janette B
authors.initials: JB
authors.lastname: Gomos
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Rowe
authors.forename: Saumendra N
authors.initials: SN
authors.lastname: Sarkar
authors.forename: Sean P
authors.initials: SP
authors.lastname: Kessler
authors.forename: Ganes C
authors.initials: GC
authors.lastname: Sen
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D019677:Artificial Gene Fusion / Q000379:methods; D003433:Crosses, Genetic; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010735:Phosphoglycerate Kinase / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C494827:Bax protein, mouse; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D010735:Phosphoglycerate Kinase; D015088:2',5'-Oligoadenylate Synthetase