Developmental aspects of sirenomelia in the mouse

The mutant gene srn produces sireniform abnormalities in the mouse. The effects of this gene on normal prenatal development were examined histologically by retrograde analysis from day 10 through day 18 of gestation. The sireniformphenotype is characterized by the fusion of the hindlimbs and accompanying defects of the posterior appendicular skeleton. Visceral defects involve the urogenital system and the lower intestinal tract. A single umbilical artery arises from the dorsal aorta and controls the fetal circulatory pathway normally mediated by the lateral umbilical arteries. This artery is believed to have resulted from the fusion of the paired primitive umbilical arteries. It is suggested that the srn mutation causes a narrowing of the posterior amnion early in development. The resulting abnormal pressure causes a dorsal displacement of the hindgut, allowing fusion of the hindlimb buds. Abnormal structural relationships and pressure in the narrowed posteriior region disrupt normal urogenital and intestinal development and increase the proximity of the primitive umbilical arteries.