Mouse inbred and congenic strains

SUMMARY Susceptibility to collagen‐induced arthritis (CIA) in mice is associated with a class II gene in MHC (Aq) but also with unknown genes outside MHC. Investigated here is the influence of genes on the X chromosome as well as the role of the X‐linked immunodeficiency (xid) mutation. Reciprocal male F1 hybrids, bred to be heterozygous or homozygous for Aq, showed a genetic influence in their susceptibility to develop CIA. Crosses were made between B10.G, B10Q, DBA/I, SWR/J, C3H.Q and CBA/Ca, and all Fi mice were castrated to avoid sex hormone modulation of the susceptibility. A differential timing of arthritis onset and severity were seen in the reciprocal F1 males. An exception was the reciprocal F1 male offspring from SWR/J and DBA/1 crosses which differed only in disease severity late in the course of the disease. The female F1 crosses did not show the same pattern of differential susceptibility to CIA as the F1 males. To exclude the possible influence the Y chromosome, F1 males of reciprocal crosses were back‐crossed to the parental strains creating offspring with equal X chromosomes but divergent Y chromosomes. No difference in development of arthritis was observed in these. The influence of the xid mutation was investigated next. The xid loci from the CBA/N mouse was bred into DBA/1 strain which is highly susceptible to CIA. The resulting congenic DBA/l‐xid strain was resistant to induction of CIA and did not develop an antibody response to type II collagen. We conclude that polymorphic genes on the X chromosome modulate susceptibility to CIA. The results from the experiments with mice carrying xid mutations confirm that such immune modulating genes exist on the sex chromosomes.

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“…The parental strains used were from different genetic backgrounds [23] of which some are susceptible to CIA (DBA/I, BIO.G. BIO.Q.…”

Section: Reciprocal F Male Micementioning

confidence: 99%

Genes on the X chromosome affect development of collagen-induced arthritis in mice

Jansson

Holmdahl

1993

Clinical and Experimental Immunology

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“…We have recently demonstrated that C57BL/10 (H-2 b ) mice are able to make a vigorous antibody response following implantation with live worms (1). B10.D2 mice are a congenic strain derived from C57BL/10 but carrying the H-2 d locus (14). This suggests that the C57BL/10 background is able to process appropriately the gp15/400 for presentation by H-2 b but not H-2 d class II molecules.…”

Section: Discussionmentioning

confidence: 99%

Fine specificity of the genetically controlled immune response to native and recombinant gp15/400 (polyprotein allergen) of Brugia malayi

1995

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Polyprotein allergens are a family of structurally homologous molecules from parasitic nematodes which induce specific immunoglobulin E in infected individuals. We show here that both H-2 and non-H-2 factors determine the ability of mice to generate T-and B-cell responses to the filarial polyprotein allergen (Brugia malayi gp15/400). Further, H-2 and non-H-2 genes can complement one another to overcome nonresponsiveness to this molecule. However, these genetic restrictions govern only responses to the native glycoprotein and all strains of mice respond equivalently when immunized with a recombinant polypeptide. Overlapping fragments of gp15/400 were constructed to compare the T-cell and antibody responses to native versus recombinant gp15/400 in responder (BALB/c H-2 d) and nonresponder (B10.D2 H-2 d , CBA H-2 k , and BALB.K H-2 k) strains. BALB/c mice generated T-cell responses to the same fragment (positions 89 to 133 and 1 to 21) whether immunized with native or recombinant material, although the antibody responses differed in fine specificity. H-2 k mice, unresponsive to the native molecule, generated T cells responsive to the centrally located peptide (positions 57 to 100) only when immunized with the recombinant. Antibody responses in H-2 k mice were directed at the peptide (positions 11 to 67) which is glycosylated in the native molecule. Our findings suggest that recognition of gp15/400 is affected by modifications that occur in the parasite but are absent when the molecule is produced in bacteria. This study provides a detailed evaluation of the immune response to an important nematode antigen as a start to the unraveling of the complex interaction of these multicellular parasites with mammalian hosts.

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“…At each generation the genes originally derived from the B6 strain are reduced by 1/2, except for the Nat gene which is identified (as the heterozygous phenotype) and preserved. Thus at the F 1 generation, B6 genes ) 1/2 1 ) 50% and at the 12th generation, N 12 , B6 genes ) 1/2 12 ) 0.024%. At this point, N 12 , Nat heterozygotes are brothersister mated and the homozygous rapid acetylator offspring are selected for breeding, to found the congenic rapid acetylator line A.B6 Nat-r .…”

Section: Congenic Inbred Strainsmentioning

confidence: 94%

“…Continuous inbreeding by mating closely related individuals results in a gradual increase in genetic homogeneity until all individuals are genetically identical (1). A strain produced by 20 or more generations of full-sib matings is defined as an inbred strain.…”

Section: Use Of Inbred Strainsmentioning

confidence: 99%

“…While it is possible (although often difficult) to do molecular analysis on genetically heterogeneous material, the use of genetically defined samples simplifies the procedures and the interpretation of the results. Isolating a molecule or sequencing a gene is only the beginning of a biological experiment; one must learn the function and regulation of the sequence in cell, tissue, and whole body (1). For example, we can clone the gene for an enzyme and transfect it into a cell.…”

mentioning

confidence: 99%

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Effects of Heredity on Response to Drugs and Environmental Chemicals: Construction of Rodent Models

Levy

Rodgers

Weber

1996

Chem. Res. Toxicol.

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Mouse inbred and congenic strains

Cited by 11 publications

References 19 publications

Genes on the X chromosome affect development of collagen-induced arthritis in mice

Genes on the X chromosome affect development of collagen-induced arthritis in mice

Fine specificity of the genetically controlled immune response to native and recombinant gp15/400 (polyprotein allergen) of Brugia malayi

Effects of Heredity on Response to Drugs and Environmental Chemicals: Construction of Rodent Models

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