Genetic Complementation in Female (BXSB × NZW)F2 Mice

Kono, Dwight H.; Park, Miyo S.; Theofilopoulos, Argyrios N.

doi:10.4049/jimmunol.171.12.6442

Cited by 14 publications

(11 citation statements)

References 26 publications

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“…Previous linkage analyses using autoimmune (NZB, MRL and BXSB) and non-autoimmune strains (NZW, C57BL and B10) did not test the combination of OPN allotypes as in the present study (MRL vs. C3H) [2,3,5] except of a few studies [4,6,17]. In the study of BXSB Â B10 crosses [4,17], to detect the loci with additive mode of inheritance in disease susceptibility might be difficult since authors used BXSB Â (B10 Â BXSB)F 1 or B10 Â (BXSB Â B10)F1 backcrosses, not F 2 crosses.…”

Section: Discussionmentioning

confidence: 67%

“…In the initial step of this study, three loci were found to be associated significantly with GN, and one of them, Agnm3, turned out to be a novel locus that did not share a chromosomal region with any lupus susceptibility loci reported previously [2][3][4][5][6]8], although some phenotypic loci referring to immune traits were reported such as Lprm4 (lymphoproliferation modifier 4, 54 cM) that was designated by spleen weight in MCN 2 mice [12] and Tsz1 (Thymus size 1, 56 cM) that was designated by thymus size [13]. It should be noted that another study using progenies from B6/lpr and MRL/lpr mice did not show any linkage of GN to Agnm3, even though we employed the same conditions for mouse breeding and histopathologic GN grading as in this study (Zhang et al, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

“…For these reasons, OPN locus might not be detected. Kono et al [6] used (BXSB Â NZW)F 2 with a different MHC haplotype combination (H-2 b and H-2 z , respectively), which might affect the difference of set of susceptibility loci possibly influenced by MHC [18]. These may be the reason why previous studies did not conclude that a locus for autoimmune diseases including glomerulonephritis and vasculitis shares a chromosomal region with Agnm3.…”

Section: Discussionmentioning

confidence: 99%

“…A study with (MRL/Mp-Fas lpr/lpr (MRL/lpr) Â Cast/Ei)F 1 Â MRL/lpr backcross mice (N 2 ) indicated GN susceptibility loci in Chr 7 and 12 [2]. Several studies with (MRL/lpr Â C57BL/6-Fas lpr/lpr (B6/lpr))F 2 mice, BXSB Â (B10 Â BXSB)F 1 backcross mice (N 2 ), (NZB Â NZW)F 2 mice, NZW Â (NZW Â C57BL/6)F 1 (N 2 ), and (BXSB Â NZW)F 2 mice indicated susceptibility loci in Chr 10, designated Lmb4 [3], Chr 1 and 3 [4], Chr 1 and 4 [5], and Chr 6 [6], respectively. It is noteworthy that the loci identified are varied and seem to depend on the parental strain of mice.…”

Section: Introductionmentioning

confidence: 99%

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Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

Miyazaki

Ono

et al. 2005

Eur J Immunol

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Potentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp-Fas lpr/lpr (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJFas lpr/lpr (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr Â C3H/lpr)F 2 mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score =4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method "cell-free system" with wheat germ ribosomes, the MRL-OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF-a, IL-1b and IFN-c in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

Miyazaki

Ono

et al. 2005

Eur J Immunol

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“…A logarithm of odds (LOD) was calculated using the LRMapqtl program. Composite interval mapping was performed using model 6 of the ZMapqtl program with options set at 2-dM intervals and a 10-cM window size, considering background loci that include unlinked and linked loci-positioned forward parameters (17,18). The experiment-wise significance level for each index was determined by analyzing 10,000 randomshuffling permutations of the actual data, and the results of chromosomes with significant and suggestive linkages (␣ Ͻ 0.01 and ␣ Ͻ 0.05, respectively) (19) for either index are shown below.…”

Section: Methodsmentioning

confidence: 99%

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice

Oishi¹,

Miyazaki²,

Mizuki³

et al. 2005

Arthritis & Rheumatism

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Objective. To analyze the influence of the genetic background of an arthritis-prone strain of mice, MRL, on the spontaneous development of arthropathy in DBA/1 mice, which histopathologically resembles enthesopathy in humans, and to clarify the strain-specific gene loci and their interactions that confer susceptibility to arthropathy.Methods. MRL, DBA/1, (MRL ؋ DBA/1)F 1 , and (MRL ؋ DBA/1)F 2 intercross mice were prepared, and the severity and onset of arthropathy of the ankle joints in individual mice were quantified (0-3 and 0-5 scale, respectively). A genome-wide scan of 271 male F 2 intercross mice with polymorphic microsatellite markers was performed.Results. Only male DBA/1, (MRL ؋ DBA/1)F 1 , and (MRL ؋ DBA/1)F 2 mice developed arthropathy. The macroscopic and histopathologic findings of arthropathy in the F 2 mice were similar to those in the parental DBA/1 mice, but the onset was significantly earlier. In the quantitative trait locus analysis of male F 2 mice, 1 susceptibility locus for both the severity and early onset of the disease in the region of an MRL allele, Amd1, was located at marker D10Mit259 (map position 40.0 cM), which was common to 1 of the sialadenitis susceptibility loci in MRL mice, Asm1. Another susceptibility locus for the severity and early onset of arthropathy in the region of a DBA allele, Amd2, was located at D3Mit46 (29.5 cM). These loci manifested an additive effect on the development of arthropathy.Conclusion. Arthropathy in DBA/1 mice is under the control of an allelic combination of gene loci, one of which is common to the locus for sialadenitis in MRL/ MpJ-lpr/lpr mice.

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Forward Genetic Approaches to Understanding Complex Behaviors

Tarantino¹,

Eisener-Dorman²

2011

Current Topics in Behavioral Neurosciences

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Assigning function to genes has long been a focus of biomedical research.Even with complete knowledge of the genomic sequences of humans, mice and other experimental organisms, there is still much to be learned about gene function and control. Ablation or overexpression of single genes using knockout or transgenic technologies has provided functional annotation for many genes, but these technologies do not capture the extensive genetic variation present in existing experimental mouse populations. Researchers have only recently begun to truly appreciate naturally occurring genetic variation resulting from single nucleotide substitutions,insertions, deletions, copy number variation, epigenetic changes (DNA methylation,histone modifications, etc.) and gene expression differences and how this variation contributes to complex phenotypes. In this chapter, we will discuss the benefits and limitations of different forward genetic approaches that capture the genetic variation present in inbred mouse strains and present the utility of these approaches for mapping QTL that influence complex behavioral phenotypes.

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Genetic Complementation in Female (BXSB × NZW)F2 Mice

Cited by 14 publications

References 26 publications

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice

Forward Genetic Approaches to Understanding Complex Behaviors

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