| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Male Reproductive Tract |
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
Traditional gene knock-out approaches using homologous recombination in embryonic stem cells are routinely used to provide functional information about genes involved in reproduction. In the present study, we examined a novel approach using N-ethyl-N-nitrosourea (ENU) together with a balancer chromosome mating strategy to identify new loci with functional roles in male fertility. Our genetic strategy is a forward-genetic approach; thus, our phenotypic investigation begins with the discovery of an abnormal phenotype without previous knowledge of the mutant locus. We isolated eight recessive mutations on chromosome 11 that resulted in male or female infertility from a screen of 184 founder pedigrees from ENU-treated males. After testing the six male infertile and two female infertile mutations for their ability to complement, we found that three independent recessive male infertile mutations failed to complement each other. The male infertility was associated with reduced epididymal sperm count, a block in late-spermatid differentiation, and increased apoptosis. Furthermore, the three male infertile mutants had severe defects in epididymal sperm morphology associated with incorrect microtubule assembly. Electron microscopy revealed unique defects in sperm head and tail morphology for each of the three alleles. One allele had an abnormal manchette assembly of the sperm head. The other two alleles had different abnormalities in the 9+2 patterning of the microtubules in the sperm tail axoneme, with one containing only five of the microtubule doublets and the other containing an extra doublet. The isolation of this allelic series identifies a new locus on mouse chromosome 11 that is required for spermiogenesis and male fertility.
2 Correspondence: Monica J. Justice, Baylor College of Medicine, One Baylor Plaza, S413, Houston, TX 77030. FAX: 713 798 1445;mjustice{at}bcm.tmc.edu
This article has been cited by other articles:
|
|
 |
|
  E. S. Maywood, S. Chahad-Ehlers, M. L. Garabette, C. Pritchard, P. Underhill, A. Greenfield, F. J. P. Ebling, R. A. Akhtar, C. P. Kyriacou, M. H. Hastings, et al. Differential Testicular Gene Expression in Seasonal Fertility J Biol Rhythms, April 1, 2009; 24(2): 114 - 125. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Lessard, H. Lothrop, J.C. Schimenti, and M.A. Handel Mutagenesis-generated mouse models of human infertility with abnormal sperm Hum. Reprod., January 1, 2007; 22(1): 159 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Furnes and J. Schimenti Fast forward to new genes in mammalian reproduction J. Physiol., January 1, 2007; 578(1): 25 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.L. Kennedy and M.K. O'Bryan N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research Hum. Reprod. Update, May 1, 2006; 12(3): 293 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.L. Kennedy, A.E. O'Connor, L.G. Sanchez-Partida, M.K. Holland, C.C. Goodnow, D.M. de Kretser, and M.K. O'Bryan A repository of ENU mutant mouse lines and their potential for male fertility research Mol. Hum. Reprod., December 1, 2005; 11(12): 871 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lorenzetti, C. E. Bishop, and M. J. Justice Deletion of the Parkin coregulated gene causes male sterility in the quakingviable mouse mutant PNAS, June 1, 2004; 101(22): 8402 - 8407. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
