Linkage study of embryopathy-polygenic inheritance of diabetes-induced skeletal malformations in the rat.
We developed an inbred rat model of diabetic embryopathy, in which the offspring displays skeletal malformations (agnathia or micrognathia) when the mother is diabetic, and no malformations when she is not diabetic. Our aim was to find genes controlling the embryonic maldevelopment in a diabetic environment. We contrasted the fetal outcome in inbred Sprague-Dawley L rats (20% skeletal malformations in diabetic pregnancy) with that of inbred Wistar Furth rats (denotedW, no skeletal malformations in diabetic pregnancy). We used offspring from the backcross F(1)×L to probe for the genetic basis for malformation of the mandible in diabetic pregnancy. A set of 186 fetuses (93 affected, 93 unaffected) was subjected to a whole genome scan with 160 micro satellites. Analysis of genotype distribution indicated 7 loci on chromosome 4, 10 (3 loci), 14, 18, and 19 in the teratogenic process (and 14 other loci on 12 chromosomes with less strong association to the malformations), several of which contained genes implicated in other experimental studies of diabetic embryopathy. These candidate genes will be scrutinized in further experimentation. We conclude that the genetic involvement in rodent diabetic embryopathy is polygenic and predisposing for congenital malformations.
Department of Neuroscience, Uppsala University, Sweden.
Niklas
N
Nordquist
Holger
H
Luthman
Ulf
U
Pettersson
Ulf J
UJ
Eriksson
D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000235:genetics; D005838:Genotype; D007569:Jaw Abnormalities / Q000235:genetics*; D008297:Male; D020412:Multifactorial Inheritance; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains
D004272:DNA, Mitochondrial