PMID- 9105782
OWN - NLM
STAT- MEDLINE
DCOM- 19970527
LR  - 20220310
IS  - 1262-3636 (Print)
IS  - 1262-3636 (Linking)
VI  - 23 Suppl 2
DP  - 1997 Mar
TI  - Are animal models of diabetes relevant to the study of the genetics of 
      non-insulin-dependent diabetes in humans?
PG  - 38-46
AB  - Although it is well-recognized that non-insulin-dependent diabetes-mellitus 
      (NIDDM) shown a strong genetic component the search for candidate genes has been 
      very difficult since NIDDM is a complex, heterogeneous, multifactorial syndrome 
      resulting from both genetic susceptibility and environmental risk factors. 
      Therefore, the use of inbred animal models is an essential component of genetic 
      investigations in this field. As these lines are genetically homogeneous, it is 
      possible to direct mating for optimal genetic crosses and control environmental 
      factors. Strains with spontaneous NIDDM may be constituted from animals with one 
      or several genetic mutation(s) transmitted generation to generation or selected 
      from non-diabetic outbred animals by repeated breeding. The ob/ob and db/db mice, 
      which are rodent models of NIDDM and obesity, belong to the first category. 
      Recent studies using the positional cloning approach allowed the mapping of ob 
      gene and identification of its product, leptin, which is a protein secreted by 
      white adipose tissue and involved in the control of food intake. The db gene 
      encodes the leptin receptor. The search for genetic linkage was undertaken in 
      polygenic models, especially the Goto-Kakisaki (GK) rat which was obtained by 
      selective breeding of individuals with glucose intolerance from a non-diabetic 
      Wistar rat colony. Though precise definition of sub-phenotypes of glucose 
      tolerance and insulin secretion, the mapping of microsatellite markers and QTL 
      analysis, it has proved possible to identify many independent loci containing 
      genes regulating glucose homeostasis and insulin secretion. In another polygenic 
      model, the OLETF rat, a locus present on chromosome X was identified. Many 
      complementary approaches in different strains may lead to the identification of 
      candidate genes for NIDDM and help direct the search for candidate genes in 
      humans who show synteny relationships with rodents.
FAU - Ktorza, A
AU  - Ktorza A
AD  - Laboratoire de Physiopathologie de la Nutrition, CNRS URA 307, Universite Paris 
      7, France.
FAU - Bernard, C
AU  - Bernard C
FAU - Parent, V
AU  - Parent V
FAU - Penicaud, L
AU  - Penicaud L
FAU - Froguel, P
AU  - Froguel P
FAU - Lathrop, M
AU  - Lathrop M
FAU - Gauguier, D
AU  - Gauguier D
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - France
TA  - Diabetes Metab
JT  - Diabetes & metabolism
JID - 9607599
SB  - IM
MH  - Animals
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - Diabetes Mellitus/genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Disease Models, Animal
MH  - *Genetic Heterogeneity
MH  - Humans
MH  - Mice
MH  - Mice, Obese
MH  - Obesity
MH  - Rats
MH  - Syndrome
RF  - 64
EDAT- 1997/03/01 00:00
MHDA- 2000/03/11 09:00
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 1997/03/01 00:00 [entrez]
PST - ppublish
SO  - Diabetes Metab. 1997 Mar;23 Suppl 2:38-46.