Trisomy 16 in the mouse fetus associated with generalized edema and cardiovascular and urinary tract anomalies

Abstract

Murine trisomy (Ts) 16 occurs in the fetal and neonatal progeny of males doubly heterozygous for the Robertsonian metacentric chromosomes Rb(16.17)7Bnr/Rb(9.16)9Rma and "all acrocentric" females. The developmental aspects of this trisomy were studied between day 12 of gestation and birth. So far, postnatal survival longer than a few hours after birth has not been observed. The frequency of Ts 16 among all implants decreased from more than 20% on day 14 to values between 4% and 7% shortly before term. Main features of Ts 16 are moderate general hypoplasia, slight developmental retardation, and cardiovascular anomalies. These latter were found in 96% of the trisomies, the great majority belonging to the transposition type, i.e., riding aorta, double outlet right ventricle (DORV) and transposition of the great arteries (TGA). Association with common atrio ventricular (AV)-canal was frequent. Other anomalies as "open eyelid", hydronephrosis, and hydroureter seem to be attributable to the effects of retardation. Generalized transient edema was frequent in the later gestational stages of Ts 16. Severe cardiovascular malformation is possible one of the factors responsible for late fetal or neonatal death in some cases. Another factor probably contributing to Ts 16 fetal mortality is insufficiency of placental function due to hypoplasia of the fetal vasculature of this organ. The teratological study of Ts 16 demands interest since evidence has been forwarded to consider this trisomy as an animal model of human trisomy 21.

Increased NCAM Expression and Vascular Development in Trisomy 16 Mouse Embryos: Relationship with Nuchal Translucency

“…Trisomy 16 mice were studied as they have nuchal edema, enlarged JLS and cardiac defects (3) Also, the mouse chromosome 16 contains the syntenic region for the human chromosome band 21q22 (9).…”

Genetic control of the survival of murine trisomy 16 fetuses

“…Between days 14 and 16 of gestation trisomy 16 fetuses t1isplay a generalized transient edema and hygroma of the back of the neck (Miyabara et al, 1982;Gearhart et al, 1986) (Figure 5). These morphologie eharacteristies were tested for thcir ability to differentiate the trisomie fetus from its normal littermate (Table 1).…”

Developmental Abnormalities in Mouse Embryos Tetrasomic for Chromosome 11: Apparent Similarity to Embryos Functionally Disomic for the X Chromosome.

“…The developmental effects of tetrasomy 16 are less serious than those of tetrasomy 11 or 15. This may be causally related to the fact that some trisomy 16 mice survive beyond parturition (Miyabara et al, 1982;Haydar et al, 1996), whereas death occurs much earlier in embryos trisomic for chromosome 11 or 15. It may be postulated that the heavier the damage caused by trisomy of a certain autosome, the severer the phenotye of its tetrasomy.…”