title: Retroposon compensatory mechanism hypothesis not supported: Zfa knockout mice are fertile.
abstract: It is hypothesized that autosomal retroposons compensate for the loss of their inactivated essential X-chromosome progenitors during spermatogenesis. Here we test this Retroposon Compensatory Mechanism (RCM) hypothesis using the Zfy gene family. The mouse autosomal retroposon Zfa is expressed in testes at the same developmental time points at which Zfx levels decline, which correspond to the time of male sex chromosome inactivation, suggesting that Zfa may compensate for the loss of Zfx during spermatogenesis. We examined the effect of Zfa-targeted mutagenesis on spermatogenesis in three genetically distinct mouse strains. Surprisingly, Zfa knockout mice showed no detectable fertility, sperm count, or testes morphology defects. We therefore conclude that Zfa is not an essential gene for spermatogenesis and fertility. This surprising finding now challenges the RCM hypothesis at least for the Zfy gene family. It also forces us to reevaluate the original data underpinning the RCM hypothesis for this family and to propose alternative hypotheses.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, British Columbia Research Institute for Children's and Women's Health, Department of Medical Genetics, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, Canada, V5Z 4H4.
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Banks
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lerner
authors.forename: Connie L
authors.initials: CL
authors.lastname: Mahaffey
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Simpson
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D005298:Fertility / Q000235:genetics* / Q000502:physiology; D018390:Gene Targeting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018626:Retroelements; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013737:Testis / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018626:Retroelements; C082035:Zfa protein, mouse