Abnormal TNF production in prediabetic BB rats is linked to defective CD45R expression
Details
Serval ID
serval:BIB_4FD712041634
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Abnormal TNF production in prediabetic BB rats is linked to defective CD45R expression
Journal
Immunology
ISSN
0019-2805 (Print)
Publication state
Published
Issued date
09/1992
Volume
77
Number
1
Pages
1-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
The genetic basis and diabetes association of aberrant tumour necrosis factor-alpha (TNF-alpha) production by activated peritoneal macrophages in diabetes-prone (dp) biobreeding (BB) rats was analysed. Southern blot analysis could not detect a restriction fragment length polymorphism for the TNF gene distinguishing dp BB rats from Wistar (Wi) rats and diabetes resistant (dr) BB rats. The contiguous genetic arrangement of lymphotoxin (LT) and TNF genes described in mouse and man was also found in the rat by cloning a chromosomal region covering both genes. In search of a polymorphic marker we amplified a (CA)n:(GT)n microsatellite in the TNF promoter region by polymerase chain reaction (PCR). We detected two alleles, (CA)26 and (CA)33, but no correlation with diabetes risk was seen. Crosses between dp BB rats and Wi or Lewis. 1A (Lew. 1A) rats, respectively, indicated that aberrant TNF-alpha production of activated macrophages is inherited dominantly with only weak penetrance. Analysis of the F2 generation and backcrosses with the two parental strains showed that aberrant TNF production co-segregates with lymphopaenia and defective CD45R expression, markers known to reflect a diabetes predisposing gene(s) outside the RT1 complex. We conclude that a single linkage group is responsible for both aberrant TNF production and defective T-cell maturation in dp BB rats.
Keywords
Animals
Antigens, CD45/*analysis
Blotting, Southern
Diabetes Mellitus, Type 1/*genetics/immunology
Female
Genes/immunology
Macrophages/immunology
Male
Polymerase Chain Reaction
Rats
Rats, Inbred BB
Rats, Inbred Lew
Rats, Inbred Strains
Tumor Necrosis Factor-alpha/*biosynthesis/genetics
Pubmed
Web of science
Create date
24/01/2008 15:39
Last modification date
20/08/2019 14:05