| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2594168 | Reproductive Toxicology | 2012 | 11 Pages |
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 (denoted W, no skeletal malformations in diabetic pregnancy). We used offspring from the backcross F1 × 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.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Pregnant diabetic W females have no fetuses with malformations. ► Diabetic L and F1 females mated with L males have 20% fetuses with malformations. ► 7 loci in the W/L genome link strongly to skeletal malformations. ► 14 loci in the W/L genome link to skeletal malformations. ► In diabetic rat pregnancy, the W/L fetal genotype is teratologically permissive and polygenic.
