Biomedical subjects

Karin Klinga-Levan

Publications and source records attributed to Karin Klinga-Levan.

5 recordsLinked to original sources

PubMed2005

RatMap--rat genome tools and data.

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

Animals↗

PubMed2004

Inconsistent susceptibility to autoimmunity in inbred LEW rats is due to genetic crossbreeding involving segregation of the arthritis-regulating gene Ncf1.

We recently identified a single-nucleotide polymorphism in the Ncf1 gene, a component of the NADPH oxidase complex, to be the cause of one of the strongest identified loci for arthritis severity in rats. This polymorphism was found to be naturally occurring in a collection of inbred rat strains as well as in wild rats. Among the inbred strains we found that different LEW substrains (LEW/Ztm and LEW/Mol), originating from different breeders, showed an allelic discrepancy in Ncf1, suggesting an impact on arthritis susceptibility between these substrains. In fact, the LEW/Mol strain was completely resistant to pristane-induced arthritis, in contrast to the LEW/Ztm strain, which was susceptible. Moreover, the LEW/Mol strain had higher production of radical oxygen species in peripheral blood leukocytes, a phenomenon most likely regulated by the polymorphisms in the Ncf1 gene. However, the phenotypic difference between LEW/Mol and LEW/Ztm is most likely a combination of several genes, of which Ncf1 is suggested to be the major regulating gene. This has also been confirmed by previous linkage analyses involving the LEW/Ztm strain which shows that a QTL on chromosome 12, most likely caused by polymorphism of Ncf1, is the major regulatory gene but that other loci are contributing. That more genes are likely to contribute was shown by a complete genome comparison of the LEW/Ztm and the LEW/Mol rat strains that uncovered an introduction of approximately 37% non-LEW genome into the LEW/Mol strain, which probably was caused by past crossbreeding. Therefore, the LEW/Mol should be regarded as a recombinant inbred strain.

Animals↗

PubMed2002

Blood group A glycosyltransferase occurring as alleles with high sequence difference is transiently induced during a Nippostrongylus brasiliensis parasite infection.

Neutral mucin oligosaccharides from the small intestine of control rats and rats infected with the parasite Nippostrongylus brasiliensis were released and analyzed by gas chromatography-mass spectrometry. Infected animals expressed seven blood group A-like structures that were all absent in the control animals. The blood group A nature of these epitopes was confirmed by blood group A reactivity of the prepared mucins, of which Muc2 was one. Transferase assays and Northern blotting on small intestines from infected animals showed that an alpha-N-acetylgalactosaminyltransferase similar to the human blood group A glycosyltransferase had been induced. The expression was a transient event, with a maximum at day 6 of the 13-day-long infection. The rat blood group A glycosyltransferase was cloned, revealing two forms with an amino acid similarity of 95%. Both types had blood group A transferase activity and were probably allelic because none of 12 analyzed inbred strains carried both types. The second type was found in outbred rats and in one inbred strain. First generation offspring of inbred rats of each type were heterozygous, further supporting the allelic hypothesis. The transient induction and the large allelic variation could suggest that glycosyltransferases are part of a dynamic system altering mucins and other glycoconjugates as a protecting mechanism against microbial challenges.

ABO Blood-Group System↗

PubMed2002

Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.

The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related ( Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.

Animals↗

PubMed1998

The Rat Gene Map.

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Journal Article↗