Genetics, Vol. 162, 307-320, September 2002, Copyright © 2002

Mutation of a Novel Gene Results in Abnormal Development of Spermatid Flagella, Loss of Intermale Aggression and Reduced Body Fat in Mice

Patrick K. Campbella,b, Katrina G. Waymirec, Robb L. Heierb,c, Catherine Sharerd,e, Diane E. Daye,f, Heike Reimanng, J. Michael Jajec, Glenn A. Friedrichh, Margit Burmeisteri, Timothy J. Bartnesse,f, Lonnie D. Russellj, Larry J. Youngd,e, Michael Zimmerk, Dieter E. Jenneg, and Grant R. MacGregorc,e
a Emory University School of Medicine, Atlanta, Georgia 30322,
b Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, Georgia 30322,
c Center for Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322,
d Department of Psychiatry, Emory University, Atlanta, Georgia 30322,
e NSF Center for Behavioral Neuroscience, Emory University, Atlanta, Georgia 30322,
f Department of Biology, Georgia State University, Atlanta, Georgia 30303,
g Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried 82152, Germany,
h Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030,
i Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109,
j Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901
k Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, 97080 Würzburg, Germany

Corresponding author: Grant R. MacGregor, University of California, Irvine, CA 92697-3940., gmacg{at}uci.edu (E-mail)

Communicating editor: C. KOZAK

ROSA22 male mice are sterile due to a recessive gene-trap mutation that affects development of the spermatid flagellum. The defect involves the flagellar axoneme, which becomes unstable around the time of its assembly. Despite a subsequent complete failure in flagellar assembly, development of the spermatid head appears normal and the spermatid head is released at the correct stage in spermatogenesis. The mutation is pleiotropic. Although ROSA22 homozygote males have normal levels of circulating testosterone and display normal mating behavior, they do not exhibit intermale aggressive behavior and have reduced body fat. The mutated gene (Gtrgeo22) maps to mouse chromosome 10 and is closely flanked by two known genes, Madcam1 and Cdc34. Ribonuclease protection analysis indicates that expression of the flanking genes is unaffected by the mutation. Gtrgeo22 is expressed at low levels in epithelial cells in several tissues, as well as in testis and brain. Analysis of the peptide coding sequence suggests that Gtrgeo22 encodes a novel transmembrane protein, which contains dileucine and tyrosine-based motifs involved in intracellular sorting of transmembrane proteins. Analysis of the Gtrgeo22 gene product should provide novel insight into the molecular basis for intermale aggression and sperm flagellar development.




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