Genetic control of fertility and embryonic waste in the mouse: A rolefor angiotensinogen.
The purpose of this study was to evaluate the impact of angiotensinogen gene (Agt) deficiency on reproductive fitness in a rodent model. Mice with 0 (Agt(-/-)), 1 (Agt(-/+)), and 2 (Agt(+/+)) copies of Agt were bred according to the following schemes: 1) Agt(-/-) x Agt(-/-), 2) Agt(-/+) x Agt(-/+), 3) Agt(+/+) x Agt(+/+), and 4) Agt(+/+) female symbol x Agt(-/+) male symbol. There were 4 breeding pairs per scheme. Breedings were time mated. Mice and litters were weighed daily. Southern blotting was used for genotyping. We found that Agt(-/-) breeding pairs had fewer litters (2 [range 1-2] vs. 4 [range 3-5]; P = 0.01), fewer pups per litter (4 [range 1-7] vs. 6 [range 1-10]; P = 0.006), and longer interpregnancy intervals (43 days [range 31-44] vs. 35.5 days [range 22-58]; P = 0.04) compared to wild-type controls. The ratio of postcoital plugs to subsequent litters was 4.0 and 1.2 for Agt(-/-) and Agt(+/+) breedings, respectively (P = 0.03). Median maternal weights during all trimesters of pregnancy were significantly lower for Agt-deficient mice compared to wild-type controls. Among Agt(-/+) x Agt(-/+) breedings, the proportions of Agt(+/+) (n = 17), Agt(-/+) (n = 38), and Agt(-/-) (n = 4) offspring differed significantly from the expected 1:2:1 Mendelian inheritance pattern (P = 0.03). Neonatal survival among the offspring derived from the Agt(-/-) x Agt(-/-) breeding scheme was significantly reduced (P = 0. 001). We conclude that Agt deficiency is associated with an in utero lethal effect, decreased fertility, and impaired neonatal survival.
Tempfer
C B
CB
Department of Obstetrics & Gynecology and Department of Human and Molecular Genetics, Baylor Collegeof Medicine, Houston, Texas 77030, USA.
Moreno
R M
RM
Gregg
A R
AR
D000022:Abortion, Spontaneous / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D020964:Embryo Loss / Q000235:genetics*; D005260:Female; D005298:Fertility / Q000235:genetics*; D005836:Genitalia, Female / Q000033:anatomy & histology; D005837:Genitalia, Male / Q000033:anatomy & histology; D005838:Genotype; D006128:Growth / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000235:genetics*; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D016019:Survival Analysis
D000808:Angiotensinogen