Autoimmunity and antibody affinity maturation are modulated by genetic variants on mouse chromosome 12

Collin, Roxanne; Dugas, Véronique; Chabot‐Roy, Geneviève; Salem, David; Zahn, Astrid; Noia, Javier M. Di; Rauch, Joyce; Lesage, Sylvie

doi:10.1016/j.jaut.2015.01.007

Cited by 4 publications

(10 citation statements)

References 40 publications

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“…We found that 3A9 TCR:insHEL NOD.B10-Chr12 congenic mice are partially resistant to diabetes (Collin et al 2015). The chromosome 12 locus did not coincide with known Idd loci but closely overlapped with Nbwa1, a locus linked to autoimmune susceptibility and autoantibody production (Rigby et al 2004).…”

Section: Introductionmentioning

confidence: 79%

“…3A9 TCR F2 mice result from the second generation intercross between B10.BR and 3A9 TCR NOD.H2 k mice. The NOD.H2 k -Chr12 congenic line was obtained by backcrossing B10.BR mice to the NOD.H2 k for eight generations as previously reported (Collin et al 2015). As two congenic sublines were derived from the NOD.H2 k -Chr12 congenic line, we hereafter refer to this line as NOD.H2 k -Chr12L, where L stand for long.…”

Section: Methodsmentioning

confidence: 99%

“…H&E and quantification of anti-HEL autoantibody levels were performed as described (Collin et al 2015;Collin et al 2014).…”

Section: Diabetes Incidencementioning

confidence: 99%

“…NOD.H2 k -Chr12 mice were generated by backcrossing for eight generations (Collin et al 2015). The resulting backcross yielded three strains.…”

Section: Diabetes-susceptible Mice Have a Lower Proportion Of Dn T Ce...mentioning

confidence: 99%

“…The chromosome 12 locus did not coincide with known Idd loci but closely overlapped with Nbwa1, a locus linked to autoimmune susceptibility and autoantibody production (Rigby et al 2004). Therefore, we exploited the NOD.B10-Chr12 congenic mice to validate the impact of this locus on autoantibody production (Collin et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines

Collin

Dugas

Pelletier³

et al. 2021

Immunogenetics

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Susceptibility to autoimmune diabetes is a complex genetic trait. Linkage analyses exploiting the NOD mouse, which spontaneously develops autoimmune diabetes, has proved to be a useful tool for the characterization of some of these traits. In a linkage analysis using 3A9 TCR transgenic mice on both B10.BR and NOD.H2 k backgrounds, we previously determined that both the Idd2 and Idd13 loci were linked to the proportion of immunoregulatory CD4 -CD8double negative (DN) T cells. In addition to Idd2 and Idd13, five other loci showed weak linkage to the proportion of DN T cells. Of interest, in an interim analysis, a locus on chromosome 12 is linked to DN T cell proportion in both the spleen and the lymph nodes. To determine the impact of this locus on DN T cells, we generated two congenic sublines, which we named Chr12P and Chr12D for proximal and distal, respectively. While 3A9 TCR:insHEL NOD.H2 k -Chr12D mice were protected from diabetes, 3A9 TCR:insHEL NOD.H2 k -Chr12P showed an increase in diabetes incidence. Yet, the proportion of DN T cells was similar to the parental 3A9 TCR NOD.H2 k strain for both of these congenic sublines. A genome-wide two dimensional LOD score analysis reveals genetic epistasis between chromosome 12 and the Idd13 locus. Altogether, this study identified further complex genetic interactions in defining the proportion of DN T cells, along with evidence of genetic epistasis within a locus on chromosome 12 influencing autoimmune susceptibility.

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Section: Introductionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

“…H&E and quantification of anti-HEL autoantibody levels were performed as described (Collin et al 2015;Collin et al 2014).…”

Section: Diabetes Incidencementioning

confidence: 99%

“…NOD.H2 k -Chr12 mice were generated by backcrossing for eight generations (Collin et al 2015). The resulting backcross yielded three strains.…”

Section: Diabetes-susceptible Mice Have a Lower Proportion Of Dn T Ce...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines

Collin

Dugas

Pelletier³

et al. 2021

Immunogenetics

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Unmet Challenges in Immune-Mediated Hepatobiliary Diseases

Beuers

Gershwin

2015

Clinic Rev Allerg Immunol

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It is ironic that the liver, which serves a critical function in immune tolerance, itself becomes the victim of an autoimmune attack. Indeed, liver autoimmunity and the autoimmune diseases associated with both innate and adaptive responses to hepatocytes and/or cholangiocytes are models of human autoimmunity. For example, in primary biliary cirrhosis, there exists a well-defined and characteristic autoantibody and considerable homogeneity between patients. In autoimmune hepatitis, there are clinical characteristics that allow a rigorous subset definition and well-defined inflammatory infiltrates. In both cases, there are defects in a variety of immune pathways and including regulatory cells. In primary sclerosing cholangitis, with its characteristic overlap with inflammatory bowel disease, there are unique defects in innate immunity and particular important contribution of lymphoid homing to disease pathogenesis. In these diseases, as with other human autoimmune processes, there is the critical understanding that pathogenesis requires a genetic background, but is determined by environmental features, and indeed the concordance of these diseases in identical twins highlights the stochastic nature of immunopathology. Unfortunately, despite major advances in basic immunology and in immunopathology in these diseases, there remains a major void in therapy. The newer biologics that are so widely used in rheumatology, neurology, and gastroenterology have not yet seen success in autoimmune liver disease. Future efforts will depend on more rigorous molecular biology and systems analysis in order for successful application to be made to patients.

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Partial retinal photoreceptor loss in a transgenic mouse model associated with reduced levels of interphotoreceptor retinol binding protein (IRBP, RBP3)

Liu

Corbett

Klaska

et al. 2018

Experimental Eye Research

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Autoimmunity and antibody affinity maturation are modulated by genetic variants on mouse chromosome 12

Cited by 4 publications

References 40 publications

Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines

Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines

Unmet Challenges in Immune-Mediated Hepatobiliary Diseases

Partial retinal photoreceptor loss in a transgenic mouse model associated with reduced levels of interphotoreceptor retinol binding protein (IRBP, RBP3)

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