Development and maintenance of ear innervation and function: lessons from mutations in mouse and man.
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Animals↗
Biomedical subjects
K Beisel
Publications and source records attributed to K Beisel.
Serologic and molecular studies of two kindreds expressing recombinant HLA DR1/DR2 haplotypes.
We have recently identified two unrelated kindreds in which DR1 and DR2 co-segregate as a single haplotype spanning several generations. Serology, PCR-RFLP and sequence-specific oligonucleotide probes were used to characterize the presence and segregation of the DRB1 and DRB5 loci in these two kindreds. In both families, the recombination resulted in co-expression of a DRB1 locus that encoded a DR1 serologic phenotype and a DRB5 locus that encoded a "short" DR2 serologic phenotype. One of these kindreds co-expressed the DR1 and DR15 (DRB5*01). The other kindred co-expressed the DR1 and DR16 (DRB5*02). Our data indicate that the recombination event occurred in the region between the DRB1 locus and the DRB5 locus. This recombinant haplotype produces a DR2 phenotype which lacks the epitopes normally encoded by the DRB1 locus, resulting in a serologic "short" antigen. The clinical significance of such a recombinational event becomes evident when patients with such a genotype require allogeneic bone marrow transplantation.
Alleles↗
Acute-phase reactants of mice. II. Strain dependence of serum amyloid P-component (SAP) levels and response to inflammation.
Serum amyloid P-component (SAP) is an acute-phase reactant of mice that occurs at baseline concentrations that vary over a 10-fold range among several common inbred mouse strains. The endogenous SAP levels of all strains increased to 180 to 230 micrograms/ml 24 h after an inflammatory stimulus of either thioglycollate (TG) or lipopolysaccharide (LPS). The C57BL/6J and C57BL/10SN strains displayed 10-fold increases in SAP concentration during acute inflammation, whereas the A/J and DBA/2J strains increased levels by only 20 to 40%. These strains were therefore designated high and low SAP responders, respectively. Testing for H-2 linkage of endogenous SAP levels by using several H-2 congenic lines derived from the C57BL/10, C3H, A, and BALB parental backgrounds indicated that the levels were only weakly influenced by the H-2 complex and were influenced much more strongly by the non-H-2 background genes. F1 hybrids (B6AF1 and B6D2F1) of high and low responder strains displayed a high SAP response similar to that of C57BL/6J mice. Because IL 1-containing macrophage supernatants and semi-purified human IL 1 were previously shown by us to induce SAP in vivo, we titrated IL 1 as LAF activity in supernatants from LPS-activated macrophages from the different mouse strains. Macrophages from the high SAP responder strains displayed significantly higher IL 1 activity than macrophages from the low SAP responder strains. LPS-unresponsive C3H/HeJ or C57BL/10Sc mice did not respond to LPS with an increase in SAP synthesis. Adoptive transfer of the SAP response to C57BL 10Sc mice by using early (90 min) acute-phase sera from the different strains indicated that higher SAP inducer activity was present in the latent phase sera from the high SAP responder strains. The identification of high and low SAP responder strains should aid in determining the biologic role of this acute-phase reactant.
Acute Disease↗
Immune recognition of serum albumin--XIV. Cross-reactivity by T-lymphocyte proliferation of subdomains 3, 6 and 9 of bovine serum albumin.
Recently, we have shown that, with rabbit antibodies against BSA, the BSA fragments 115-184, 307-285 and 505-582 (essentially corresponding to subdomains 3, 6 and 9 of BSA) exhibit a cross-reaction which increases remarkably with the time antisera are obtained after the initial immunization. In the present report, we have examined whether this cross-reaction at the B-cell level takes place also at the T-cell level. Optimum conditions for T-cell proliferation to BSA and the three fragments were determined in terms of priming dose, challenging dose, time lymph nodes are obtained after immunization and finally duration of culture. Several strains of mice representing independent haplotypes and recombinant strains were examined for their responsiveness to BSA by T-lymphocyte proliferation, performed in the respective preimmune sera of the same mice. This afforded the identification of high- and low-responder strains to BSA. It was determined that the immune response to BSA is controlled by genes in the I-A subregion of the H-2 gene complex with some slight non-H-2 influences. In order to avoid the possibility of genetic exclusion of response to a given antigenic site and to improve the change of total site recognition, two high-responder strains (B10.M and B10.G) were crossed. Antibodies raised in (B10.M X B10.G)F1 mice recognized subdomains 3, 6 and 9 and these were found to be cross-reactive. Specific 125I-labelled antibodies isolated on a given subdomain-adsorbent were bound very well by adsorbents of the other two subdomains. T-cells from the F1 mice that had been primed with subdomain 3 responded to subdomain 3 and were also high responders to subdomain 6 and intermediate responders to subdomain 9. After priming with subdomain 6, the T-cells responded equally as well to subdomains 3 or 6 and slightly to subdomain 9. Finally, priming with subdomain 9, gave T-cells that responded to subdomain 9 and also gave high responses to subdomains 3 or 6. It was concluded that the cross-reactions originally observed at the B-cell level also take place at the T-cell level.
Animals↗
T-cell regulation in autoimmune thyroiditis.
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Animals↗
Genetic studies of the murine corneal response to Pseudomonas aeruginosa.
The murine genetic control of resistance to Pseudomonas aeruginosa eye infection previously has been demonstrated to be regulated by two complementing dominant genes, PsCR1 and PsCR2. The PsCR1 locus apparently is not associated with the H-2 complex, whereas the PsCR2 locus could not definitively be associated with H-2. In this study we attempted to demonstrate a possible H-2 linkage of the PsCR2 locus. A panel of inbred congenic strains varying with either the H-2 haplotype or genetic background from inbred partners of C57BL/10, C3H, A, and BALB/c strains were characterized for their P. aeruginosa infectivity phenotypes. These studies indicated that the PsCR2 locus is not associated with the H-2 locus. Furthermore, variations of the H-2 haplotype did not change the resistance patterns observed in these strains. However, BALB.B and BALB.K congenic lines were resistant to P. aeruginosa eye infection, whereas BALB/cJ mice were susceptible. Examination of hybrids (BALB.K X BALB/cJ)F1 and (BALB.B X BALB/cJ)F1 demonstrated that an autosomal dominant gene(s), PsCR, confers resistance. Segregation analysis for the H-2 haplotype and the PsCR gene in offspring of backcross matings with the BALB/cJ parental strain suggested that this PsCR gene is not linked to the H-2 complex and has an inheritance pattern of a single locus or several tightly linked loci.
Animals↗
Genetic factors controlling the susceptibility to experimental autoimmune thyroiditis in inbred rat strains.
CDF (high responder) rats were crossed with SHR (low responder) rats to study genetic factors influencing susceptibility to experimental autoimmune thyroiditis (EAT). F1 hybrid rats showed intermediate susceptibility to thyroiditis. Gene segregation patterns of F2 and backcross rats demonstrated that the immune response to rat thyroglobulin (RaTg) is under polygenic control. A main factor controlling immune response to RaTg is associated with the X chromosome. Females of CDF and SHR rats produced higher levels of antibody, suggesting that antibody production to RaTg is a sex-influenced trait. Different genetic control mechanisms are evident in autoantibody production and thyroid lesions. No evidence of linkage of an immune response gene to RaTg to the major histocompatibility complex of the rat (RT1) was observed.
Animals↗