Disease relevance of Igh-C

• The murine situs inversus viscerum (iv) gene responsible for visceral asymmetry is linked tightly to the Igh-C cluster on chromosome 12 [1].
• Among congenic BALB/c mice differing only at Igh-C allotype loci, variations in responsiveness were found in both delayed-type hypersensitivity and lymphocytes proliferation assays, indicating a possible role for Igh-C loci-linked genes [2].
• A DNA sequence that generates aberrantly rearranged immunoglobulin heavy chain constant region genes in murine plasmacytomas is shown to participate in a chromosome translocation [3].
• Fv-4, a gene controlling susceptibility to ecotropic murine leukemia viruses, was linked to both Pre-I (prealbumin) and Igh-I (immunoglobulin heavy-chain constant region) loci on chromosome 12 in mice [4].

Psychiatry related information on Igh-C

• These results have implications both for network interactions in the immune response and for the genetic basis of Igh-C linked Id expression [5].

High impact information on Igh-C

• 5' flanking region of immunoglobulin heavy chain constant region genes displays length heterogeneity in germlines of inbred mouse strains [6].
• CSR changes the immunoglobulin heavy chain constant region (CH) gene being expressed from Cmu to other CH genes, resulting in a switch of the immunoglobulin isotype from IgM to IgG, IgE or IgA [7].
• 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 [8].
• Identification of Igh-C-linked determinants on suppressor T cell hybrids and factors specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) [9].
• The specificity of RF was apparently further controlled by genes linked to but different from the Igh-C locus, as indicated by the absence of IgG2aa-specific RF in one of the 6 Igh-1a strains tested [10].

Biological context of Igh-C

• Because several markers and a tentative map has been constructed for the Igh complex on chromosome 12 in BXD mice, we suggest that the gene that controls BCG-induced anergy is located on the centrometric side of Igh-C approximately 18 to 28 recombination units [11].
• Genetic and structural analyses of the mouse genes encoding constant region of immunoglobulin subclass (Igh-C) have shown that recombination is rare within this cluster which is inherited as a set designated the Igh haplotype [12].
• The characteristic ratio of IgG2a and IgG2b isotypes persisted during the whole period of the primary and secondary antibody response of CBA and CBA-Igb Igh-C congenic mice [13].
• Distinct allelic forms of each Igh-C locus could be defined by restriction fragment length polymorphism (RFLP) [14].
• These loci are located in a tightly linked cluster between the immunoglobulin heavy chain constant region gene cluster, Igh-C, and the serum prealbumin locus Pre-1, in this manner: centromere--Igh-C--(Tthy, Tind)-Tsu-Tpre--Pre-1 [15].

Anatomical context of Igh-C

• The data are discussed in terms to T cell enhancement of IgG2a Ab synthesis being mediated through T cell enhancement of the Igh-C gene switching mechanism within TNP-Ficoll-responsive B cell clones [16].
• Our results have suggested that IgG anti-DNA responses occurring as a result of polyclonal B cell activation during the course of malaria infection markedly differs quantitatively and clonotypically among murine strains and appear to be controlled at least in part by the Igh-C gene or gene(s) closely linked to it [17].
• Chimeric mice are constructed by reconstituting lethally irradiated mice with peritoneal cells (PerC) and bone marrow cells from congenic pairs of mice differing in Igh-C allotype [18].
• Two kinds of circular DNA were identified in the lymph nodes as excision products of switch recombination of immunoglobulin heavy-chain constant region (CH) genes [19].
• The positions of nuclear matrix anchorage regions (MARs) have been mapped within the 200 kb mouse immunoglobulin heavy chain constant region locus, thereby allowing an estimate of the size of DNA domains within a segment of the genome [20].

Associations of Igh-C with chemical compounds

• T15 idiotype expression in the murine response to phosphorylcholine is actively regulated by genes linked to the Igh-C locus [21].

Physical interactions of Igh-C

• This map confirms genetically the localization of the Igh-V gene complex distal to Igh-C on the chromosome [22].
• Recent studies have established genetic linkage between iv and the immunoglobulin heavy chain gene complex (Igh-C), located on distal mouse chromosome 12 [23].
• In mice, two genetic regions, the major histocompatibility complex (H-2) and the immunoglobulin heavy chain constant region, were shown to regulate the production of anti-gliadin antibody [24].

Regulatory relationships of Igh-C

• Furthermore, they suggest that the 11-5 IdX markers identified are shared by alloantibodies of the BALB/c (Igh1a) and A.TH (Igh1e) mouse strains and may be expressed independently of Igh-C allotype markers [25].

Other interactions of Igh-C

• On the basis of these results the Igh-Ox marker is tentatively placed between Igh-C and the rest of the Igh-V markers [26].
• Analysis of the allele distribution in an interspecific mouse backcross by single-strand conformation polymorphism positioned the chromogranin A locus on Chromosome 12, between Igh-C and D12Pas1 [27].
• The Tsu(d) gene is located very near the heavy chain constant-region genes, Igh-C, on the side toward the prealbumin gene, Pre-1 [28].
• Our analysis of the variable region genes of MRL mice showed that the MRL/lpr D genes were similar to those of the C3H mouse (Igh-C allotype j) [29].
• In the present study, we have refined the genetic map location of iv relative to the breakpoint of a reciprocal translocation, T(5;12)31H, involving the telomeric region of chromosome 12 distal to Igh-C and the proximal region of chromosome 5 [23].

Analytical, diagnostic and therapeutic context of Igh-C

• Spurred by a recent report that mapped the iv gene to mouse chromosome 12 which was not excluded by our previous work, we used the polymerase chain reaction on our larger cohort to determine that the iv gene is indeed linked tightly to the Igh-C locus on this chromosome: we observed 0/156 recombinants between the iv and Igh-C loci [1].

References