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W Kastern

Publications and source records attributed to W Kastern.

25 records · Page 2Linked to original sources
PubMed1986

Genetic heterogeneity in the major histocompatibility complex of various BB rat sublines.

Fragments of cloned rat class I transplantation antigen genes were used to define the polymorphism detected between two lines of closely related BB rats. One line, BB-Hagedorn (BB/H), is prone to diabetes, and the other (BB control) is resistant. A cDNA probe representing part of the second extracellular domain of a class I antigen detected several DNA fragments and revealed a 2kb fragment present in resistant, but absent in diabetes-prone, BB/H rat DNA following digestion with BamH1. A 40 bp cDNA probe from the same domain showed a further simplified pattern in the DNA hybridization analysis. Only two fragments, 15 kb and 7 kb, were present in the resistant rats; the diabetes-prone BB/H rats lacked the 7 kb fragment. Several lines of evidence suggest that the gene contained in this 7 kb fragment may be deleted. Analysis of other diabetic BB rats and in the F2 generation of intercross offspring of F1 hybrid parents following crossbreeding between the resistant (BB-control) and diabetes-prone (BB/H) line demonstrate that the class I polymorphism was not linked directly to diabetes. Examination of various other BB lines and sublines indicate that these polymorphisms can be traced back to at least one other subline (Worcester) in the parent colony.

Animals↗
PubMed1986

A deletion in a rat major histocompatibility complex class I gene is linked to the absence of beta 2-microglobulin-containing serum molecules.

Class I major histocompatibility antigens are composed of a heavy chain that is noncovalently associated with beta 2-microglobulin (beta 2m). Most class I molecules are membrane bound, but mouse and rat cDNA clones and genes without a functional code for the transmembrane amino acids have been identified. The membrane-associated class I molecules are important in the control of cell-mediated cytotoxicity, while the function of the soluble molecules remains unclear. Previous studies have shown that beta 2m circulates in rat serum in three different molecular weight classes. The first is free beta 2m (Mr, 12,000), the second is about Mr 70,000, and the third is roughly Mr 200,000. In an inbred subline of immunodeficient, diabetes-prone BioBreeding rats (BioBreeding/Hagedorn), previous work detected two restriction fragment polymorphisms in class I major histocompatibility complex genes, one of them a gene deletion on a 7-kilobase BamHI fragment and the other on a 2-kilobase BamHI fragment. In these rats we have found that the third serum beta 2m-binding size class is absent. Analysis of F1 and F2 individuals following cross-breeding between BioBreeding/Hagedorn rats and genetically related (nondiabetic) control BioBreeding w-subline rats demonstrated that the large-size serum peak of beta 2m was associated with the presence of the class I restriction fragments.

Animals↗
PubMed1985

Immunological aspects of type 1 and 2 diabetes mellitus.

IDDM occurs predominantly among individuals being class II antigen HLA-DR 3 and/or 4 positive, while NIDDM is not associated with HLA-D. Although the HLA-DR 3 or 4 specificities are prerequisites for IDDM to develop, their high frequencies (about 60%) in the background population preclude tissue typing as a predictive test, underlined by the observation that less than 50% of monozygotic twins are concordant for IDDM. The presence of a number of immune abnormalities argues that the causes of IDDM may be sought in an altered immune reaction against antigens present in the pancreatic B cells and/or in the environment. The majority of IDDM patients of short duration show both cellular and humoral autoimmunity against the pancreatic B cells. Similar phenomena may be observed in patients initially diagnosed as NIDDM and treated with oral hypoglycemic agents. It has been speculated that these patients have a retarded form of IDDM. It is possible that the combination of specific Class II antigen molecule(s) and an invading antigen (virus, bacterium, chemical etc.) presented to the immune system triggers the formation of effector cells such as B lymphocytes and cytotoxic T lymphocytes which also cross-react with the pancreatic B cells. Multiple exposures to this or related antigens throughout several years may eventually lead a sufficient loss of pancreatic B cells to cause insulin dependence.

Antibody Formation↗
PubMed1985

Characterization of two class I major histocompatibility rat cDNA clones, one of which contains a premature termination codon.

A cDNA clone that shares considerable homology with mRNA for class-I major-histocompatibility (MHC) antigens has been isolated from a cDNA library constructed from an insulin-secreting tumor of the NEDH rat (RIN). Although there is very strong homology between the third extracellular domain of this gene, and other class-I antigen genes, a stop codon was noticed at the junction between the external and transmembrane regions of its protein. Thus, this gene codes for a truncated class-I antigen that lacks both transmembrane and cytoplasmic domains but has hydrophilic amino acids towards its C-terminus and therefore resembles a soluble protein. This gene was found to be transcribed at significant levels in the rat testis and an insulin-secreting tumor, but transcription was negligible in liver and kidney. The partial nucleotide sequence of this gene in a Wistar rat genomic clone indicates that the cDNA clone is represented in the rat genome complete with premature termination codon, thus eliminating the possibility of artifactual origins for the clone.

Animals↗
PubMed1985

Identification of an HLA-DQ beta-chain related genomic sequence associated with insulin-dependent diabetes.

Restriction fragment length polymorphism detected by a cDNA probe for an HLA-DQ beta-chain gene has revealed a HLA-DR4 linked BamH1 3.7 kb fragment which is rarely found among insulin-dependent diabetic patients. The present analysis demonstrates that the BamH1 3.7 kb fragment present on a HLA-DR4 positive chromosome in a healthy individual contains coding sequences for an HLA-DQ beta-chain gene and that the absence of this fragment among HLA-DR4 positive insulin-dependent patients is due to the loss of a BamH1 restriction within an intervening sequence.

Base Sequence↗
PubMed1984

Restriction fragment polymorphisms in the major histocompatibility complex of diabetic BB rats.

DNA isolated from diabetic BB (BB/Hagedorn) rats was examined for restriction fragment length differences within the major histocompatibility complex (MHC) as compared with nondiabetic (W-subline) BB rats. Polymorphisms were detected using a mouse class I MHC gene as probe. Specifically, a 2-kb BamHI fragment was present in all the nondiabetic rats examined, but absent in the diabetic rats. Similar polymorphisms were observed with various other restriction enzymes, particularly XbaI, HindII, and SacI. There were no polymorphisms detected using either a human DR-alpha (class II antigen heavy chain) or a human DC-beta (class II antigen light chain) gene as probes. These results indicate that the BB rat diabetic syndrome may be linked to differences in class I MHC genes.

Animals↗