Disease relevance of Hbb

• Thus, inheritance of at least one C57L allele at the albino or Hbb loci was associated with protection against MNU-induced lymphoma development [1].
• We report a mouse model of type I Usher syndrome, rd5, whose linkage on mouse chromosome 7 to Hbb and tub has homology to human Usher I reported on human chromosome 11p15 [2].
• This localization places Cckbr in the same region as the mouse obesity mutation tubby (tub), which also maps near Hbb (2.4 +/- 1.4 cM) [3].
• Polymerase chain reaction analysis of DNA extracted from papillomas devoid of stromal contamination by fluorescence-activated sorting of single cell dispersions immunolabeled with anti-keratin 13 antibody revealed loss of heterozygosity at the Hbb locus, demonstrating that this event occurs during premalignant stages of tumor development [4].
• In the present study, by combining Southern blot and polymerase chain reaction fragment length polymorphism analyses, we detected complete loss of heterozygosity at the beta-globin (Hbb) locus, distal to Ha-ras-1, in 15 of 20 (75%) skin carcinomas [4].

High impact information on Hbb

• These findings are consistent with the presence of a putative tumor suppressor gene linked to the Hbb locus in the 7F1-ter region of mouse chromosome 7, the functional inactivation of which may constitute a critical event in skin tumor progression, possibly during the malignant conversion stage [4].
• Submapping of this anonymous clone across a panel of 27 smaller deletions localized D7OR1 distal to a chromosomal subregion important for survival of the preimplantation embryo, proximal to globin [beta-chain (Hbb)], and near the shaker-1 (sh-1) locus [5].
• Its linkage to Hbb and c places it in the same region of the chromosome as Mod-2, the structural gene for mitochondrial malic enzyme [6].
• In experiments designed to detect new mutations affecting hemoglobin, we irradiated the male or female parent in reciprocal crosses of two mouse strains that differ in alleles at the hemoglobin (Hba, Hbb) loci as well as at five other specific loci [7].
• We have shown that the bulk of the difference in susceptibility between BSVS and salmonella-resistant A/J mice is the result of a genetic difference at a single locus not closely linked to H-2, Igh-C, or Hbb, and not X-linked [8].

Biological context of Hbb

• Deletion mapping of four loci defined by N-ethyl-N-nitrosourea-induced postimplantation-lethal mutations within the pid-Hbb region of mouse chromosome 7 [9].
• Haplotypes of the beta-globin gene complex (Hbb) in laboratory mice have been defined as d, p, and s [10].
• Segregation analysis of nucleotide sequence polymorphisms in interspecific backcross progeny revealed linkage of mCd19 with hemoglobin beta (Hbb), Int-2, and H19, other loci previously mapped to the same region of mouse chromosome 7, confirming the localization of mCd19 to this region [11].
• However, no linkage of low responsiveness to the Hbb locus was evident, an area present at a more distal site to the centromere on the same chromosome [12].
• The genetic basis for erythrocyte osmotic fragility differences between mouse strains C57BL/6 and DBA/2 was examined through analyses of their serial backcross progeny, recombinant inbred (ri) strains (BXD), and congenic C57BL/6 strains with allelic differences at Hbb or Fv-2 [13].

Anatomical context of Hbb

• N-ethyl-N-nitrosourea mutagenesis of a 6- to 11-cM subregion of the Fah-Hbb interval of mouse chromosome 7: Completed testing of 4557 gametes and deletion mapping and complementation analysis of 31 mutations [14].
• The specific-locus test was performed with N-ethyl-N-nitrosourea (ENU) on spermatogonia of mice by using visible loci and a hemoglobin beta-chain (Hbb) locus [15].
• We therefore used the GFP transgenic model in combination with allelic variants of CD45 and the hemoglobin beta (Hbb) chain to develop a model system that allows all blood lineages to be followed in a mouse model of bone marrow transplantation (BMT) [16].
• The T cell alloantigens A.R.T.-1, A.R.T.-2, Pta, Ag-F and RT-Ly-2 were examined for linkage to albinism and the haemoglobin variant Hbb, and for cell expression similarities in the rat [17].

Associations of Hbb with chemical compounds

• Simplified typing of mouse hemoglobin (Hbb) phenotypes using cystamine [18].

Physical interactions of Hbb

• An N-ethyl-N-nitrosourea (ENU)-induced mutation in the Hbb-b1 gene of the mouse hemoglobin-beta complex (Hbb) has been shown to result in a high-oxygen affinity hemoglobin, homologous with hemoglobin Rainier in man (Peters, J., et al., Genetics 110:709, 1985) [19].

Other interactions of Hbb

• Deletion mutations at the albino (c) locus have been useful for continuing the development of fine-structure physical and functional maps of the Fes-Hbb region of mouse chromosome 7 [20].
• This locus is designated Hma (HPRT mobility alteration) and maps very close to the Hbb locus [21].
• One thousand fifty-two mice were analyzed for a protein polymorphism segregating for the distal flanking marker, beta-globin (Hbb), and 13 recombinants between Hbb and sh-1 were identified [22].
• Three loci (Es-3, Hbb and Mod-1) had low levels of polymorphism in 1981 and had become monomorphic by 1990 [23].
• The genetic distances between the loci examined, calculated from the recombination frequencies, suggested that mCd19 was located centrally between Hbb and H19 [11].

Analytical, diagnostic and therapeutic context of Hbb

• To detect Hbb variant molecules, we developed a new protocol based on high-performance liquid chromatography that is sensitive and precise, allowing rapid and quantitative analysis of erythroid chimerism [16].
• The genetic relationship between the Hbb locus and body size in a population of mice divergently selected for six-week body weight [24].

References