GLUCOCORTICOID-INDUCED CLEFT PALATE IN THE MOUSE: TWO MAJOR HISTOCOMPATIBILITY COMPLEX, H-2, LOCI WITH DIFFERENT MECHANISMS

Genetics ◽  
1983 ◽  
Vol 103 (2) ◽  
pp. 263-276
Author(s):  
Joseph J Bonner ◽  
Marvin L Tyan

ABSTRACT Isolated cleft palate is induced in the progeny of pregnant mice that are given glucocorticoids. The incidence varies among inbred strains and with dose and stage of gestation when the drug is given. One chromosomal region responsible for strain-associated differences in sensitivity is the major histocompatibility complex, H-2. H-2a is associated with susceptibility, H-2b with resistance. There appear to be both maternal and embryonic genetic factors affecting the sensitivity to glucocorticoids. In experiments reported here congenic strains of mice with H-2a, H-2d and H-2k haplotypes on a C57BL/10 genomic background were used. This allowed the determination of the effect on sensitivity by two H-2 subregions; the subregions are H-2K to I-E and I-C to H-2D. Methods included dose-response analysis and reciprocal cross analysis using dexamethasone given on day 12 of pregnancy. Results show that each subregion affects the strain's sensitivity to dexamethasone-induced cleft palate. The regression coefficients for B10.A-H-2a (45.4 ± 4.13) were different from those for B10.BR-H-2k (67.2 ± 10.8) and B10.D2-H-2d (70.5 ± 9.74). The estimated mean arcsine% cleft palate at 160 mg/kg was different for each strain: B10.A-H-2a, 53.1 ± 2.19; B10.BR-H-2k, 33.1 ± 2.27; B10.D2-H-2d, 25.0 ± 2.75. Different patterns of change in sensitivity were observed among the reciprocal crosses. In summary, the H-2K to I-E subregion seemed to influence both maternal and embryonic factors, whereas only embryonic factors were influenced by the I-C to H-2D subregion. These data suggest that the mechanisms affecting glucocorticoid sensitivity which are genetically encoded within each H-2 subregion are different, and there is an interaction between the alleles. The mode of interaction can be either complementation or epistasis.

2015 ◽  
pp. 213-221
Author(s):  
J. Hors ◽  
J. Gony ◽  
J. M. Andrieu ◽  
J. P. Cesarini ◽  
F. Teillet ◽  
...  

1979 ◽  
Vol 150 (4) ◽  
pp. 755-760 ◽  
Author(s):  
K Yamazaki ◽  
M Yamaguchi ◽  
L Baranoski ◽  
J Bard ◽  
E A Boyse ◽  
...  

Previous studies of mating preference signified that mice can sense one another's major histocompatibility complex (MHC) types, probably by olfaction. This conclusion has now been substantiated by the use of a Y-maze whose two arms were differentially scented with currents of air conducted through boxes occupied by B6 (H-2b) males and by B6-H-2k congenic males. Four B6 mice, two males and two females, were successfully trained, by water deprivation and reward, to enter the arm scented by B6 or B6-H-2k males. One of the males and one of the females were trained to select the B6-scented arm; the other male and female were trained to select the B6-H-2k-scented arm. Untrained mice showed no MHC discrimination in the maze. The performance of the trained mice in distinguishing between MHC congenic homozygous F2 segregants derived from a cross of B6-H-2k with B6 was as good as their performance in distinguishing the respective inbred strains, thus essentially eliminating alternative and significant additional explanations of MHC-associated sensory discrimination. The data further indicate that chemosensory discrimination of MHC types can be entirely dissociated from sex differences and from the circumstances of mating.


1985 ◽  
Vol 162 (6) ◽  
pp. 1878-1891 ◽  
Author(s):  
W C Watson ◽  
A S Townes

Analysis of the IgG autoantibody subclass response in the collagen II autoimmune arthritis (CII AIA)-susceptible D1 strain mice revealed that the onset of disease was associated with a predominance of IgG2a autoantibody. In a comparative study, resistance in the B6 strain was associated with a deficient IgG2a autoantibody response. B6 IgG1, 2b, and 3 autoantibody responses generally overlapped those of arthritic D1 mice, and estimates of antibody crossreactivity and affinity were similar for both strains. In crosses between D1 and B6, arthritis developed only in those F1 mice with IgG2a autoantibody responses approximating or exceeding those in arthritic D1 mice. Additional studies with B6 and B10 strains suggested an alternate role for the IgG2b autoantibody response. In inbred strains with known genetic backgrounds, a dissociation between the magnitude of the total IgG autoantibody response and the percent of total as IgG2a was demonstrated. The H-2q, Ig-1c D1 strain was a high-total and high-percent IgG2a responder, while the H-2d, Ig-1c D2 strain was a low-total but high-percent IgG2a responder. The H-2b, Ig-1b B6 strain was a low-total and low-percent IgG2a responder, while the H-2b/q, Ig-1b/c (B6D1)F1 hybrid was a low-total but high-percent IgG2a responder. A further dissociation between high-percent IgG2a autoantibody responsiveness and the H-2 haplotype was demonstrated by the H-2 congenic B10.D2/n (H-2d, Ig-1b) strain, in which a low-percent IgG2a response was observed to differ from the D2 strain. High-percent IgG2a autoantibody responsiveness also appeared to be inherited as a dominant trait based upon high responses in all (B6D1)F1 hybrids and backcrosses to D1. These findings suggest that the H-2 haplotype is involved in the total IgG autoantibody response but that the relative fraction of the total response as IgG2a is independent of the H-2 haplotype and possibly related to Igh-C genes. C5-deficient SWR (H-2q, Ig-1c) mice were found to have a high total autoantibody response to mouse CII and IgG2a comparable to arthritic D1 mice, but these mice did not develop arthritis. Based upon these observations, we conclude that susceptibility to CII AIA requires the interaction of multiple genes, both major histocompatibility complex (MHC) and non-MHC, which influence the magnitude (total IgG) and the quality (IgG subclass) of the autoimmune response and the availability of appropriate mediators (C5) to initiate the inflammatory reaction.


1995 ◽  
Vol 18 (1) ◽  
pp. 48-49
Author(s):  
Jeffrey B. Blount ◽  
Takeshi Kondoh ◽  
Lisa L. Pundt ◽  
John Conrad ◽  
Elizabeth M. Jansen ◽  
...  

AbstractIn contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.


1993 ◽  
Vol 177 (1) ◽  
pp. 9-17 ◽  
Author(s):  
W T Golde ◽  
T R Burkot ◽  
S Sviat ◽  
M G Keen ◽  
L W Mayer ◽  
...  

The causative agent of Lyme disease, Borrelia burgdorferi, is transmitted by ticks of the Ixodes ricinus complex. In this study, we report the antibody response of recombinant inbred strains of mice of the H-2, b, d, and k haplotypes, infected with B. burgdorferi as a result of exposure to infected I. dammini. The patterns of antibody response assayed by Western blot analysis indicate significant major histocompatibility complex (MHC) restriction to bacterial antigens within the first 2 mo of infection in mice. Other bacterial antigens induce a significant response across the MHC haplotypes tested when assayed on the same bacterial strain used to transmit the infection, but do not crossreact with the same proteins derived from heterologous strains of B. burgdorferi. No response to outer surface protein A was detected at any time during the 60-d period we analyzed this infection. A third group of bacterial antigens appear to generate a MHC-nonrestricted response, and this lack of restriction is maintained when assaying the crossreactivity of the response with other strains of B. burgdorferi. These proteins may provide more accurate diagnostic probes than those currently in use. Finally, there appears to be a significant difference in the expression of most bacterial antigens when the spirochete is cultured for many passages since the same strain of bacterium isolated from low-passage and high-passage preparations exhibit different banding patterns in Western blots when assayed with the same sera.


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