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E F Remmers

Publications and source records attributed to E F Remmers.

At least 37 records · Page 2Linked to original sources
PubMed1999

Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats.

The present study attempts to identify specific genetic loci contributing to experimental autoimmune uveoretinitis (EAU) susceptibility in F2 progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F2 progeny of F344/N x LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptor retinoid-binding protein (IRBP). A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in selected F2 animals that developed severe eye disease or remained unaffected to identify phenotype:genotype co-segregation. The F2 population (n = 1287) demonstrated a wide range of histologically assessed EAU scores (assessed on a scale of 0-4). The disease incidence and severity were not consistent with a simple Mendelian inheritance model. Of the F2 hybrid rats, 60% developed EAU, implying the existence of a potent susceptibility locus with incomplete penetrance associated with the LEW genome or a more complex polygenic model of inheritance. Two genomic regions, on chromosomes 4 and 12, showed strong genetic linkage to the EAU phenotype (P < 0.0016), suggesting the presence of susceptibility loci in these chromosomal regions. In conclusion, we have identified two genomic candidate intervals from D4Arb8 to D4Mit17 on chromosome 4 and from the chromosome end to D12Arb8 on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analysis of these genomic regions may lead to identification of the susceptibility genes and to characterization of their function.

Animals↗
PubMed1998

Localization of quantitative trait loci regulating adjuvant-induced arthritis in rats: evidence for genetic factors common to multiple autoimmune diseases.

Adjuvant-induced arthritis (AIA) in rats is a widely used autoimmune experimental model with many features similar to rheumatoid arthritis (RA). To identify potential genetic regulatory mechanisms in RA, we conducted genome-wide linkage analysis in F2 progeny of arthritis-susceptible Dark Agouti (DA) and relatively resistant Fischer 344 (F344) inbred rats. We compared the data with our previously reported investigation of collagen-induced arthritis (CIA), which was expanded in the follow-up study reported in this work. We found two quantitative trait loci (QTLs) in common, i.e., Aia1/Cia1 on chromosome 20, which includes the MHC, and Aia3/Cia3 on chromosome 4. We also identified a second unique QTL in AIA, Aia2, on chromosome 4. Interestingly, the QTL region on chromosome 4 (Aia3/Cia3), like the MHC, appears to be involved in several other autoimmune diseases in rats, including insulin-dependent diabetes, thyroiditis, and experimental autoimmune uveitis. Moreover, an analysis of conserved synteny among rats, mice, and humans suggested that Aia2 and Aia3/Cia3, like Aia1/Cia1, contain candidate genes for several autoimmune/inflammatory diseases in mice and humans, including diabetes, systemic lupus erythematosus, inflammatory bowel disease, asthma/atopy, multiple sclerosis, and RA. The rat models appear to provide a powerful complementary approach to identify and characterize candidate genes that may contribute to autoimmune diseases in several species.

Animals↗
PubMed1998

Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats.

OBJECTIVE: To identify novel non-major histocompatibility complex (non-MHC) genetic loci controlling the severity of homologous rat type II collagen-induced arthritis (CIA). METHODS: We conducted a genome-wide scan to identify CIA regulatory quantitative trait loci (QTL) in an F2 cross between DA (CIA highly susceptible) and ACI (CIA resistant) inbred rats immunized with homologous rat type II collagen (RII). These strains share the MHC/RT1av1 haplotype required for susceptibility to RII-induced CIA. RESULTS: F2 females had higher median arthritis scores than did males. Relative resistance in the males was determined by inheriting either a DA or an ACI Y chromosome and was independent of the source of the X chromosome. In addition, a major QTL was localized on chromosome 2 (Cia7, logarithm of odds score 4.6). Cia7 is in a region that shows linkage conservation with chromosomal regions that regulate autoimmune diabetes and experimental autoimmune encephalomyelitis in mice and multiple sclerosis in humans. CONCLUSION: Sex chromosomes and Cia7 play an important role in regulating CIA in response to RII. This rat model should facilitate positional cloning and functional characterization of regulatory genes that may play a role in several forms of autoimmune disease, including rheumatoid arthritis.

Animals↗
PubMed1996

The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12.

A genomic DNA fragment containing the rat epimorphin gene sequence was cloned from a rat DNA cosmid library using a mouse epimorphin cDNA probe. Within the cosmid insert, nine epimorphin exons were identified and sequenced. The predicted amino acid sequence of the rat epimorphin protein exhibited 96 and 86% identity with the mouse and human epimorphin proteins, respectively. Consistent with the developmentally related expression pattern of the mouse epimorphin gene, transcripts of the rat epimorphin gene were detected in 17-day postfertilization rat embryos. The gene, designated Epim, was assigned to rat chromosome 12 by somatic cell hybrid analysis and localized to 12q16 by fluorescence in situ hybridization. The mouse and human homologs of this gene were localized on mouse chromosome 5 and human chromosome 7 by linkage analysis and chromosomal in situ hybridization, respectively.

Amino Acid Sequence↗
PubMed1996

A simplified, competitive RT-PCR method for measuring rat IFN-gamma mRNA expression.

We describe an adaptation of competitive RT-PCR to quantitate rat IFN-gamma mRNA expression. An IFN-gamma DNA mimic that shared the same primers and had an identical sequence to the target mRNA except for deletion of 66 nucleotides was created by a simple PCR amplification from target cDNA. To reduce variations of initial RNA concentrations, beta-actin cDNAs from each target RNA sample were normalized using the densitometric data. A known amount of pretitrated DNA competitor was then used to analyze the relative levels of target cDNA in different samples by PCR co-amplification. The amplification efficiency for both target and competitor remained constant throughout the PCR reaction, and the ratio of target to competitor PCR product remained proportional to the initial ratio of target to competitor. Relative mRNA levels among samples determined by this method were comparable to levels determined by northern blot analysis. They were also comparable to levels of IFN-gamma protein estimated by ELISA. We conclude that this method can be used to estimate the relative abundance of the target mRNA. This method is adaptable to quantitation of other cytokines and is particularly valuable if there are numerous samples or if the amount of initial mRNA is limited.

Animals↗
PubMed1996

Genetic maps of polymorphic DNA loci on rat chromosome 1.

Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, gamma-aminobutyric acid receptor beta3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor beta1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that a large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19.

Animals↗
PubMed1996

Linkage maps of rat chromosomes 15, 16, 17, 19, and X.

Linkage maps of rat chromosomes 15, 16, 17, 19, and X were constructed by multipoint genetic linkage analysis of 22 polymorphic markers in 40 F2 progeny of Fischer (F344/N) and Lewis (LEW/N) inbred rat strains. These markers are associated with eight genes (angiotensin receptor A, M3 muscarinic acetylcholine receptor, heme oxygenase, endothelin receptor A, haptoglobin, tyrosine aminotransferase, phosphoribosylpyrophosphate synthetase subunit II, and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) and 14 anonymous loci. Linkage analysis placed the markers into five linkage groups covering 11.7,7.9,11.6,42.5, and 5.1cM. These linkage groups were assigned to rat chromosomes 15, 16, 17, 19, and X, respectively, either by mouse x rat somatic cell hybrid analysis or based on previously identified locations of severalloci. In polymorphism analysis, these markers exhibited two to nine different alleles in 16 inbred rat strains.

Alleles↗
PubMed1996

Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10.

Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN. +/op) F1 carriers, we mapped this locus by linkage analysis with microsatellite markers to rat chromosome 10. The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]-1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog-2, and proline-rich protein). The markers for these loci include nine not previously reported. The op locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its location, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect.

Animals↗
PubMed1996

A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats.

Identification of specific genetic loci that contribute to susceptibility to rheumatoid arthritis (RA) in humans has been hampered by several factors, including: i) multiple interacting genetic loci contributing to susceptibility; ii) complex interactions of environmental and genetic factors; iii) genetic heterogeneity; and iv) low penetrance. We have, therefore, mapped quantitative trait loci (QTLs) that control inflammatory arthritis susceptibility and/or severity in progeny of two inbred rat strains with significantly different susceptibilities to collagen-induced arthritis (CIA), an animal model for RA. Not surprisingly, we identified a major susceptibility factor, Cia1, on chromosome 20 in the vicinity of the rat major histocompatibility complex (MHC). However, by limiting the analysis to animals with arthritis-susceptible MHC genotypes and using genome-wide QTL analytic techniques, we also found four non-MHC QTLs-Cia2, 3, 4 and 5-on chromosomes 1, 4, 7 and 10, that contributed to disease severity. In addition, a QTL on chromosome 8 was suggestive for linkage. Characterization of the genes underlying these QTLs will facilitate the identification of key biochemical pathways regulating experimental autoimmune arthritis in rats and may provide insights into RA and other human autoimmune diseases. These genes may also represent novel targets for therapy.

Animals↗
PubMed1995

A genetic map of microsatellite markers on rat chromosome 7.

Nine microsatellite loci were mapped to rat Chromosome (Chr) 7 by genetic linkage and somatic cell hybrid analysis. These loci include the gene encoding a member of the IID sub-family of cytochrome P450 (Cyp2d), a gene with repetitive sequences expressed during myotube formation (D7Arb1e), four anonymous loci, D7Arb81, D7Arb208, D7Arb569, D7Arb609a, and three DNA loci defined by MapPair markers R245, R513, and R1071. The nine loci were all identified by PCR-based microsatellite polymorphism analysis and were characterized in 40 F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) rats for segregation analysis. These markers formed a single linkage group spanning 76.8 cM with the following order and distances: D7Arb569-11.4 cM-D7Arb81-9.7 cM-R513-2.6 cM-Cyp2d-0.0 cM-R245-1.3 cM-D7Arb1e-10.4 cM-R1071-15.9 cM-D7Arb609a-15.4 cM-D7Arb208. Physical mapping of Cyp2d by somatic cell hybrid analysis allowed us to assign this linkage group to rat Chr 7. For each marker, two to six alleles were detected in a panel of 16 inbred rat strains (ACI/N, BN/SsN, BUF/N, DA/Bkl, F344/N, LER/N, LEW/N, LOU/MN, MNR/N, MR/N, SHR/N, SR/Jr, SS/Jr, WBB1/N, WBB2/N, WKY/N).

Alleles↗
PubMed1995

Genetic map of 16 polymorphic markers forming three linkage groups assigned to rat chromosome 4.

Sixteen polymorphic markers, including markers for eight new loci, forming three linkage groups, were assigned to rat Chromosome (Chr) 4 by linkage analysis of the progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. One gene, Igk, was mapped by restriction fragment length polymorphism (RFLP) analysis. One marker for Tcrb was identified by the polymorphic insertion of a repetitive LINE element. The remaining 14 markers contained polymorphic simple sequence repeats (SSRs). Ten were identified in genes (Tgfa, Npy, Prss1, Prss2, Aldr1, Iapp, Prp, Eno2, Cacnl1a1, and Il6), one was identified in a sequence related to a gene (Egr4l1), and three were identified in anonymous DNA segments. The SSR markers were highly polymorphic in 16 inbred rat strains. These markers expand the genetic map of the rat and should be useful in future genetic studies of inbred rats.

Animals↗
PubMed1995

Genetic map of eight microsatellite markers comprising two linkage groups on rat chromosome 6.

Five genes and three anonymous DNA loci were mapped to rat chromosome 6 by genetic linkage and somatic cell hybrid analyses. The eight loci were all identified by PCR-based microsatellite polymorphism analysis and were characterized in 40 F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) inbred rats for segregation analysis. These markers formed two linkage groups spanning, respectively, 58.1 cM and 4.0 cM. The first linkage group is comprised of two anonymous DNA loci and four genes with the following map order and distances: D6Cep8 (previously D3)-17.9 cM-D6Arb309-2.5 cM-Vsnl1 (neural visinin-like protein)-20.4 cM-Prkar2b (type IIb regulatory subunit of cAMP-dependent protein kinase)-8.8 cM-Fkhl1 (forkhead-like transcription factor BF-1)-8.5 cM-Rnu1c (18-3A U1 RNA). The second linkage group is comprised of one gene, Ckb (creatine kinase, brain) and one anonymous DNA locus, D6Arb54, separated by 4.0 cM. For each marker, two to eight alleles were detected in a panel of 16 inbred rat strains (ACI/N, BN/SsN, BUF/N, DA/Bk1, F344/N, LER/N, LEW/N, LOU/MN, MNR/N, MR/N, SHR/N, SR/Jr, SS/Jr, WBB1/N, WBB2/N, and WKY/N). Comparative mapping information indicated that rat chromosome 6 exhibits syntenic conservation with mouse chromosome 12. Homologs of the rat chromosome 6 loci have been identified on human chromosomes 2, 7, and 14.

Animals↗