| Title: | A pair of mouse KRAB zinc finger proteins modulates multiple indicators of female reproduction |
| Address: | "Department of Human Genetics, University of Michigan Medical School, 1241 E. Catherine St., Ann Arbor, MI 48109-5618, USA" |
| DOI: | 10.1095/biolreprod.109.080846 |
| ISSN/ISBN: | 1529-7268 (Electronic) 0006-3363 (Print) 0006-3363 (Linking) |
| Abstract: | "Kruppel-associated box-zinc finger proteins (KRAB-ZFPs) are the largest class of transcriptional regulators in mammals, yet few have been assigned biological roles. Cloning the genes underlying the regulator of sex-limitation (rsl) phenotype, in which the normally male-specific sex-limited protein (SLP) is expressed in female mice, identified two KRAB-ZFPs, Rsl1 and Rsl2, as influencing sexually dimorphic liver gene expression. Combined absence of both repressors in rsl mice leads to increased expression in female liver of major urinary proteins (MUPs) and certain enzymes of steroid metabolism, as well as SLP. We hypothesized that this altered gene expression might affect reproductive physiology in rsl females. Urinary MUP (uMUP) concentration varied with the estrous cycle in both wt and rsl females but was consistently higher in rsl urine. A behavioral odor test revealed that wild-type (wt) males preferred rsl to wt females, possibly due to elevated uMUPs providing greater pheromone presentation. To ascribe activity to Rsl1, Rsl2, or both, the genes were individually expressed as liver-specific transgenes. RSL2 overexpression accentuated uMUP fluctuations across the estrous cycle, whereas RSL1 overexpression did not. In addition, puberty onset, as indicated by vaginal opening (VO), occurred 2 days earlier in rsl females, and excess RSL2, but not RSL1, restored VO timing to wt. Hence, transcriptional repression by RSL in liver modifies female mouse reproduction via targets that likely impact both hormonal and pheromonal cues. The large and rapidly diversifying KRAB-ZFP family may modulate biological processes, including reproduction, to confer individual differences that may isolate populations and ultimately lead to speciation" |
| Keywords: | "Animals Biomarkers/metabolism Estrous Cycle/genetics/metabolism/physiology Female *Gene Expression Regulation/genetics Liver/metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Pheromones/metabolism Protein Isoforms/genetics/metabolism/physiology Pro;" |
| Notes: | "MedlineKrebs, Christopher J Robins, Diane M eng P60 DK020572/DK/NIDDK NIH HHS/ R01 DK053998/DK/NIDDK NIH HHS/ R01-053998/PHS HHS/ 5P60DK-20572/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural 2010/01/01 Biol Reprod. 2010 Apr; 82(4):662-8. doi: 10.1095/biolreprod.109.080846. Epub 2009 Dec 30" |
