Identification of the Gasa3 and Gasa4 autoimmune gastritis susceptibility genes using congenic mice and partitioned, segregative and interaction analyses

Silveira, Pablo A.; Wilson, Wendy E.; Esteban, Luis; Jordan, Margaret A.; Hawke, Christine G; Driel, Ian R. van; Baxter, Alan G.

doi:10.1007/s00251-002-0482-4

Cited by 3 publications

(5 citation statements)

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“…Gasa3 was assigned to a region near D6Mit149 on chromosome 6 but has not been experimentally verified while Gasa4 mapped to the H2 locus. An analysis of congenic mice revealed that BALB mice heterozygous at H2 (H2 b/d ) developed a two-fold higher incidence of autoimmune gastritis compared to homozygous mice (H2 b or H2 d ) [48]. This confirmed the assignment of Gasa4 to the H2 locus.…”

Section: Genetic Susceptibility To Autoimmune Gastritissupporting

confidence: 57%

“…Two minor autoimmune gastritis susceptibility loci have also been identified [48]. Gasa3 was assigned to a region near D6Mit149 on chromosome 6 but has not been experimentally verified while Gasa4 mapped to the H2 locus.…”

Section: Genetic Susceptibility To Autoimmune Gastritismentioning

confidence: 97%

“…A study utilising a (BALB/ cBy Â C57BL/6By) cross found that a gene/s near the minor histocompatibility antigen 27 (H27) on chromosome 5 was genetically linked with susceptibility to autoimmune gastritis [46]. However, this association could not be confirmed in subsequent studies [47,48]. The second study utilised a (BALB/cCrSlc Â DBA/2CrSlc) cross and found genetic linkage of the Mls-1 gene on chromosome 1 with susceptibility to autoimmune gastritis [49].…”

Section: Genetic Susceptibility To Autoimmune Gastritismentioning

confidence: 99%

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Extrathymic mechanisms of T cell tolerance: Lessons from autoimmune gastritis

Hogan

Ang

Gleeson

et al. 2008

Journal of Autoimmunity

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Section: Genetic Susceptibility To Autoimmune Gastritissupporting

confidence: 57%

Section: Genetic Susceptibility To Autoimmune Gastritismentioning

confidence: 97%

Section: Genetic Susceptibility To Autoimmune Gastritismentioning

confidence: 99%

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Extrathymic mechanisms of T cell tolerance: Lessons from autoimmune gastritis

Hogan

Ang

Gleeson

et al. 2008

Journal of Autoimmunity

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“…49 Similarly, the QTL influencing IL-6 on Chr 6 (41.5 cM) is close to a previously mapped QTL on Chr 6 (44 cM) for autoimmune gastritis, 50 collagen II-induced arthritis (Chr 6, 48.7 cM), 51 and cutaneous hypersensitivity (Chr 6, 45.5 cM). 52 These results suggest that these regions on mouse Chrs 9 and 6 contain a gene or a cluster of genes that not only influence the proinflammatory response to Ad, but also other inflammatory processes in mice.…”

Section: (C) Ifn-g Is Plotted Against Tnf-a As Described In (B) (D) mentioning

confidence: 88%

Identification of multiple genetic loci that regulate adenovirus gene therapy

et al. 2003

Gene Ther

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A key aspect of the immune response to adenovirus (Ad) gene therapy is the generation of a cytotoxic T-cell (CTL) response. To better understand the genetic network underlying these events, 20 strains of C57BL/6 Â DBA/2 (BXD) recombinant inbred (RI) mice were administered with AdLacZ and analyzed at days 7, 21, 30, and 50 for liver b-galactosidase (LacZ) expression and CTL response. Sera levels of interferon gamma (IFN-g), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) were analyzed at different times after AdLacZ. There was a distinct strain-dependent expression of LacZ, which was strongly correlated with the CTL response. Among the five BXD RI strains that exhibited significantly prolonged LacZ expression, four also exhibited a marked defect in the production of Ad-specific CTL. There was a strong correlation between the sera levels of IFN-g, TNF-a, and IL-6, but cytokine responses were not significantly correlated with LacZ expression or the CTL response. Quantitative trait loci regulating LacZ on day 30 were found on chromosome (Chr) 19 (33 cM) and Chr 15 (42.8 cM). Cytotoxicity mapped to Chr 7 (41.0 and 57.4-65.2 cM), Chr 15 (61.7 cM), and Chr X (27.8 cM). IFN-g production mapped to Chr 18 (22, 27, and 32 cM) and Chr 11 (64.0 cM). TNF-a and IL-6 production mapped to Chr 6 (91.5 cM) Chr 9 (42.0 cM) and Chr 8 (52 and 73.0 cM). These results indicate that different strains of mice exhibit different pathways for effective clearance of AdLacZ depending on genetic polymorphisms and interactions at multiple genetic loci.

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“…For example, 87% of D3Tx female A/J mice develop AOD, but only 6% develop autoimmune gastritis (AG), whereas 17% of female BALB/cJ mice show signs of AOD and 33% develop AG. Genetically, D3Tx-induced AOD (30 -32) and AG (33,34) have been the most well characterized. Recently, we established that AOD is controlled by multiple interacting quantitative trait loci (QTL) (Aod1-Aod5, H2, and Gasa2) (32).…”

mentioning

confidence: 99%

Aod1Controlling Day 3 Thymectomy-Induced Autoimmune Ovarian Dysgenesis in Mice Encompasses Two Linked Quantitative Trait Loci with Opposing Allelic Effects on Disease Susceptibility

Roper

McAllister

Biggins

et al. 2003

The Journal of Immunology

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Day 3 thymectomy (D3Tx) leads to a paucity of CD4+CD25+ suppressor T cells, a loss of peripheral tolerance, and the development of organ-specific autoimmune disease in adult mice. Importantly, D3Tx does not lead to autoimmune disease in all mouse strains, indicating that this process is genetically controlled. Previously, we reported linkage of D3Tx-induced autoimmune ovarian dysgenesis (AOD) and its intermediate phenotypes, antiovarian autoantibody responsiveness, oophoritis, and atrophy, to five quantitative trait loci (QTL), designated Aod1 through Aod5. We also showed interaction between these QTL and H2 as well as Gasa2, a QTL controlling susceptibility to D3Tx-induced autoimmune gastritis. To physically map Aod1, interval-specific bidirectional recombinant congenic strains of mice were generated and studied for susceptibility to D3Tx-induced AOD. Congenic mapping studies revealed that Aod1 controls susceptibility to oophoritis and comprises two linked QTL with opposing allelic effects. Aod1a resides between D16Mit211 (23.3 cM) and D16Mit51 (66.75 cM) on chromosome 16. Aod1b maps proximal of Aod1a between D16Mit89 (20.9 cM) and D16Mit211 (23.3 cM) and includes the candidate genes stefin A1, A2, and A3 (Stfa1-Stfa3), inhibitors of cathepsin S, a cysteine protease required for autoantigen presentation, and the development of autoimmune disease of the salivary and lacrimal glands following D3Tx. cDNA sequencing revealed the existence of structural polymorphisms for both Stfa1 and Stfa2. Given the roles of cathepsins in Ag processing and presentation, Stfa1 and Stfa2 alleles have the potential to control susceptibility to autoimmune disease at the level of both CD4+CD25+ suppressor and CD4+CD25− effector T cells.

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Identification of the Gasa3 and Gasa4 autoimmune gastritis susceptibility genes using congenic mice and partitioned, segregative and interaction analyses

Cited by 3 publications

References 0 publications

Extrathymic mechanisms of T cell tolerance: Lessons from autoimmune gastritis

Extrathymic mechanisms of T cell tolerance: Lessons from autoimmune gastritis

Identification of multiple genetic loci that regulate adenovirus gene therapy

Aod1Controlling Day 3 Thymectomy-Induced Autoimmune Ovarian Dysgenesis in Mice Encompasses Two Linked Quantitative Trait Loci with Opposing Allelic Effects on Disease Susceptibility

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