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Molecular and Cellular Biology, August 2002, p. 5554-5562, Vol. 22, No. 15
0270-7306/02/$04.00+0 DOI: 10.1128/MCB.22.15.5554-5562.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Testis-Specific Cytochrome c-Null Mice Produce Functional Sperm but Undergo Early Testicular Atrophy
Sonoko Narisawa,1 Norman B. Hecht,2 Erwin Goldberg,3 Kelly M. Boatright,1 John C. Reed,1 and José Luis Millán1*
The Burnham Institute, La Jolla, California 92037,1
Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania 19104,2
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 602083
Received 15 November 2001/
Returned for modification 28 January 2002/
Accepted 30 April 2002
Differentiating male germ cells express a testis-specific form of cytochrome c (Cyt cT) that is distinct from the cytochrome c expressed in somatic cells (Cyt cS). To examine the role of Cyt cT in germ cells, we generated mice null for Cyt cT. Homozygous Cyt cT-/- pups were statistically underrepresented (21%) but developed normally and were fertile. However, spermatozoa isolated from the cauda epididymis of Cyt cT-null animals were less effective in fertilizing oocytes in vitro and contain reduced levels of ATP compared to wild-type sperm. Sperm from Cyt cT-null mice contained a greater number of immotile spermatozoa than did samples from control mice, i.e., 53.1% ± 13.7% versus 33.2% ± 10.3% (P < 0.0001) for vas deferens sperm and 40.1% ± 9.6% versus 33.2% ± 7.5% (P = 0.0104) for epididymal sperm. Cyt cT-null mice often exhibit early atrophy of the testes after 4 months of age, losing germ cells as a result of increased apoptosis. However, no difference in the activation of caspase-3, -8, or -9 was detected between the Cyt cT-/- testes and controls. Our data indicate that the Cyt cT-null testes undergo early atrophy equivalent to that which occurs during aging as a consequence of a reduction in oxidative phosphorylation.
* Corresponding author. Mailing address: The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 646-3130. Fax: (858) 713-6272. E-mail: millan{at}burnham.org.
Molecular and Cellular Biology, August 2002, p. 5554-5562, Vol. 22, No. 15
0022-538X/02/$04.00+0 DOI: 10.1128/MCB.22.15.5554-5562.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.