| First Author | Spearow JL | Year | 1997 |
| Pages | 166 (Abstr.) | Mgi Jnum | J:44129 |
| Mgi Id | MGI:1099380 | Citation | Spearow JL, et al. (1997) Mapping reproductive QTL in backcrosses and reproductive congenic strains of mice. :166 (Abstr.) |
| abstractText | Full text of Abstract: MAPPING REPRODUCTIVE QTL IN BACKCROSSES AND REPRODUCTIVE CONGENIC STRAINS OF MICE. Jimmy L. Spearow, Heshaam Fallah, Nathalie Zayek, Iskra Banova, Marty Reed, Sal Sariano, Binh Le, Brian Orelli, Binh Nguyen, Thi Duong, Marylynn Barkley. Section of Neurobiology, Physiology & Behavior, Univ. or California at Davis, CA. This study mapped quantitative trait loci (QTL) controlling major genetic differences in hormone- induced ovulation rate (HIOR) and hormone-induced ovarian aromatase activity (HIAA) in mice. Aromatase is a critical enzyme regulating reproduction that converts androgens into estrogens. C57BL/6J (B6) mice showed 6-fold higher HIOR and 21-fo1d higher HIAA than A/J mice. QTL linkage analysis in a (B6A)XA Bx population mapped suggestive HIOR QTL to Chromosome (Chr) to Chr 9 near Cyp-19 (Hior-1) to Chr 2 near D2Mit433 (Hior-2) to Chr 6 near D6Mit316 (Hior-3), and to Chr X near DXMit22 (Hior-4) (LODÕs=1.98 to 2.74). QTL linkage analysis using composite mapping (Zeng Model 6) showed that the HIOR QTL near D6Mit316 was significant (LOD=3.45). QTL linkage analysis of another (B6A)XA Bx population mapped an HIAA QTL to Chr 4 near D4Mit16 (Hiaa-1) (LOD=3.93), and a suggestive HIAA QTL to Chr 2 near D2Mit17 (Hiaa-2) (LOD-2.01). Publication of these studies has been greatly hindered by the marginal LOD scores observed for these low heritability traits. The genetic noise caused by the simultaneous segregation of several reproductive QTL also hindered the detection of each QTL. Therefore, reproductive congenic strains were developed for regions of mouse Chr 2, 4, 6, 9, and X by repeatedly back-crossing mice with B6 microsatellite markers at and flanking each reproductive QTL onto the A/J genetic background. These reproductive congenic strains of mice were used to confirm the presence of HIOR QTL on Chr 2, 6 and X, and to confirm the presence of HIAA QTL on Chr 2 and 4. Further analysis of congenic testcrosses revealed that 1) the Chr 6 HIOR QTL maps as a single QTL (P<0.001); 2) the Chr 2 HIAA QTL seems to be due to 2 separate QTLs flanking the original backcross map position, with the proximal QTL near D2Mit355 and a more distal QTL; and 3) the Chr 4 HIAA QTL seems to be due to two linked QTL (P<0.01) with opposite effects that flank the QTL position estimated in the original backcross data set. Studies are now in progress to high resolution map, positionally clone, and characterize these confirmed reproductive QTL. Biochemical activity, RT PCR and inununoblotting studies of A/J and B6 parentals, and AXB, BXA RI strains have also revealed major genetic differences in the induction and maintenance of aromatase. The present data show that genetic differences in the hormonal induction of ovarian steroidogenesis, follicle maturation and ovulation are a major source of variation in the regulation of reproduction. Consideration of these genetic differences will improve the control of ovarian and reproductive function. Molecular genetic markers for reproductive QTL will be useful for: 1) diagnosing reproductive disorders; 2) determining optimal hormonal treatments for achieving the desired level of reproduction for diverse hormone-response genotypes in many mammalian species, including humans; and, 3) selecting for improved reproductive performance in economically important species. Supported by USDA 89-37240-4909; PHS R01-HD28253; NSF IBN 95-07872. |
