The mutation of the LEW.1AR1-iddm rat maps to the telomeric end of rat chromosome 1.
The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes mellitus (T1DM) with an autosomal recessive mode of inheritance. T1DM susceptibility loci could be localized on chromosome (RNO) 20 in the major histocompatibility complex region (Iddm1) and on RNO1 (Iddm8, Iddm9) in a BN backcross cohort. In this study the impact of the different susceptibility regions on diabetes development was investigated in a backcross population of the diabetes-resistant PAR strain. A cohort of 130 [(PAR x LEW.1AR1-iddm) x LEW.1AR1-iddm] N2 rats was monitored for blood glucose and analyzed by linkage analysis. Sixteen percent of the PAR backcross animals developed T1DM. Genetic analysis revealed significant linkage to T1DM in the MHC region on RNO20p12. In contrast to the linkage analysis of the BN backcross cohort, only one susceptibility locus for T1DM could be identified on RNO1. This susceptibility region on RNO1 mapped to the telomeric end corresponding to Iddm8. Eighty-nine percent of diabetic PAR backcross animals were homozygous for Iddm8. The Iddm9 diabetes susceptibility region showed no linkage to diabetes in the PAR backcross cohort. The data of this study provide evidence that the mutation leading to T1DM in the LEW.1AR1-iddm rat is located at the telomeric end of RNO1 corresponding to Iddm8.
Weiss
Heike
H
Institute of Clinical Biochemistry, Hannover Medical School, 30623, Hannover, Germany, heike.weiss@med.uni-rostock.de.
Arndt
Tanja
T
Jörns
Anne
A
Lenzen
Sigurd
S
Cuppen
Edwin
E
Hedrich
Hans J
HJ
Tiedge
Markus
M
Wedekind
Dirk
D
D000818:Animals; D033481:Chromosomes, Mammalian / Q000737:chemistry / Q000235:genetics*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D007178:Inbreeding; D008285:Major Histocompatibility Complex; D009154:Mutation; D020161:Physical Chromosome Mapping; D051381:Rats; D011913:Rats, Inbred BB; D016615:Telomere / Q000737:chemistry / Q000235:genetics*