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a Department of Obstetrics & Gynecology and
b Department of Human and Molecular Genetics, Baylor Collegeof Medicine, Houston, Texas 77030
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+/+ 
x Agt-/+ 
. 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.
1 This study was supported by Erwin-Schroedinger-Auslandsstipendium J1592MED with funding by the Fonds Zur Foerderung der Wissenschaftlichen Forschung (to C.T.); National Institute of Child Health and Human Development (NICHD) Grant R03-HD-34667-01 (to A.R.G.); Methodist Hospital Foundation Grant (to A.R.G.).
2 Correspondence: Anthony R. Gregg, Department of Gynecology and Obstetrics, Baylor College of Medicine 6550 Fannin-Suite 901, Houston, TX 77030. Fax: 713 798 6956; agregg{at}bcm.tmc.edu
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