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Linkage study of embryopathy-Polygenic inheritance of diabetes-induced skeletal malformations in the rat

Nordquist, Niklas; Luthman, Holger LU ; Pettersson, Ulf and Eriksson, Ulf J. (2012) In Reproductive Toxicology 33(3). p.297-307
Abstract
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 F-1 x 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... (More)
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 F-1 x 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. (C) 2011 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Rat, Diabetes-in-pregnancy, Streptozotocin, Congenital anomalies, Mandible, Whole genome scan, Micro satellites, Genetic predisposition
in
Reproductive Toxicology
volume
33
issue
3
pages
297 - 307
publisher
Elsevier
external identifiers
  • wos:000303361200005
  • scopus:84859739848
ISSN
1873-1708
DOI
10.1016/j.reprotox.2011.12.009
language
English
LU publication?
yes
id
7d256812-1536-47ec-8a5b-4cafef64cc56 (old id 2562974)
date added to LUP
2012-06-01 08:44:17
date last changed
2017-01-01 06:14:32
@article{7d256812-1536-47ec-8a5b-4cafef64cc56,
  abstract     = {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 F-1 x 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. (C) 2011 Elsevier Inc. All rights reserved.},
  author       = {Nordquist, Niklas and Luthman, Holger and Pettersson, Ulf and Eriksson, Ulf J.},
  issn         = {1873-1708},
  keyword      = {Rat,Diabetes-in-pregnancy,Streptozotocin,Congenital anomalies,Mandible,Whole genome scan,Micro satellites,Genetic predisposition},
  language     = {eng},
  number       = {3},
  pages        = {297--307},
  publisher    = {Elsevier},
  series       = {Reproductive Toxicology},
  title        = {Linkage study of embryopathy-Polygenic inheritance of diabetes-induced skeletal malformations in the rat},
  url          = {http://dx.doi.org/10.1016/j.reprotox.2011.12.009},
  volume       = {33},
  year         = {2012},
}