Isolation and mapping of four new DNA markers from mouse chromosome 4.
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Animals↗
Biomedical subjects
B A Mock
Publications and source records attributed to B A Mock.
The gene for lysyl oxidase maps to mouse chromosome 18.
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Animals↗
Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization.
Phosphate-activated glutaminase is found in mammalian small intestine, brain, and kidney, but not in liver. The enzyme initiates the catabolism of glutamine as the principal respiratory fuel in the small intestine, may synthesize the neurotransmitter glutamate in the brain, and functions in the kidney to help maintain systemic pH homeostasis. Interleukin-9 (IL9) is a relatively new cytokine that supports the growth of helper T-cell clones, mast cells, and megakaryoblastic leukemia cells. cDNA clones have recently been obtained for each of these genes. The human loci for phosphate-activated glutaminase (GLS) and IL9 have previously been mapped to chromosomes 2 and 5, respectively, by analysis of somatic cell hybrid DNAs. By using chromosomal in situ hybridization, we have regionally mapped GLS to 2q32----q34 and IL9 to 5q31----q35.
Animals↗
IL9 maps to mouse chromosome 13 and human chromosome 5.
Mouse and human cDNA clones encoding the T-cell and mast cell growth factor P40, now designated IL-9, were used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between inbred strains of mice and interspecific backcross progeny. Segregation of mouse and human chromosomes among somatic cell hybrids indicated a location on mouse chromosome 13 and human chromosome 5. RFLPs were identified among inbred strains of mice. Analysis of chromosome 13 alleles for Tcrg, Dhfr, and Il-9 in an interspecific cross between Mus musculus and NFS/N or C58/J mice indicates that IL9 is distal to Tcrg and proximal to Dhfr.
Alleles↗
Molecular genetic markers spanning mouse chromosome 10.
Somatic cell hybrids, recombinant inbred (RI) strains, and progeny of an intersubspecific backcross were typed by Southern blot analysis to prepare a linkage map of mouse chromosome 10. The seven genetic markers in this map, four of which had not previously been positioned, include genes involved in oncogenesis (Gli, Myb, Tra-1), proviral integration (Emv-25), and immune responses (Ifg, Ifgr, Pfp). The linkage map spans much of the chromosome and covers a region of the mouse genome with few molecular markers. The gene order established here demonstrates that the genes for murine interferon-gamma (Ifg) and its receptor (Ifgr) are at opposite ends of the chromosome and that Ifgr and the Myb oncogene are closely linked, a factor that may be related to their joint transcriptional enhancement in some plasmacytoid lymphosarcomas.
Animals↗
Gene mapping of the three subunits of the high affinity FcR for IgE to mouse chromosomes 1 and 19.
The high affinity receptor for IgE (Fc epsilon RI) is a tetrameric structure consisting of a single IgE-binding alpha subunit, a single beta subunit, and two disulfide-linked gamma subunits. The alpha subunit of Fc epsilon RI and most Fc receptors are homologous members of the Ig superfamily. By contrast, the beta and gamma subunits from Fc epsilon RI are not homologous to the Ig superfamily. The gamma-chains do share a region of high homology with the zeta-chain of the TCR. No homology has been found to date for beta with any published sequence. Here, we report that a single copy gene encodes Fc epsilon RI beta and that the locus for Fc epsilon RI beta is found on mouse chromosome 19, genetically linked to the Ly-1 (Ly-12) locus and in a region that also contains Ly-10 and Ly-44 (CD20). Homology comparisons among these molecules reveal limited regions of homology between Fc epsilon RI beta and Ly-44 (CD20) as well as other striking similarities: both molecules have four putative transmembrane segments and a probably topology where both amino- and carboxytermini protrude into the cytoplasm. In addition, we show that a single gene for FC epsilon RI gamma is found at the distal end of mouse chromosome 1, clustered in a region where Fc epsilon RI alpha has also been linked to Fc gamma RII. At least one of the two forms of Fc gamma RII has recently been shown to contain gamma subunits identical to the gamma subunits of Fc epsilon RI. The close association of the genes for Fc epsilon RI alpha, FC gamma RII, and their shared gamma subunits raises interesting implications regarding coordinate regulation of gene expression.
Amino Acid Sequence↗
Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.
We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.
Amino Acid Sequence↗
The murine Il-6 gene maps to the proximal region of chromosome 5.
Murine Il-6 cDNAs were isolated by cross-hybridization with a human IL-6 cDNA from an IL-1 activated bone marrow stromal cell line (W20). Mouse-hamster somatic cell hybrids were utilized to localize murine Il-6 to chromosome 5. Genetic mapping with respect to En-2, AlbH, and Gus in backcross progeny from an interspecific mating between C57BL/6J and Mus spretus positioned Il-6 3 cM distal to En-2. The syntenic relationships of Il-6 and En-2 in mouse and man, as well as the potential role of IL-6 in tumorigenesis, are discussed.
Amino Acid Sequence↗
The role of plasmacytoma growth factor in the in vitro responses of murine plasmacytoma cells.
Many plasmacytomas arising in BALB/c mice are dependent upon a specific, macrophage-derived plasmacytoma growth factor for survival and proliferation in vitro. Adherent cells taken from the peritoneal oil granuloma in which the early plasmacytomas arise and proliferate produce 50 times more PCT-GF activity in vitro than do normal peritoneal cells, thus suggesting a possible in vivo role for PCT-GF. Purification and amino acid sequencing of PCT-GF derived from the murine macrophage cell line, P388D1, have identified a 23 kDa protein with a unique NH2-terminal sequence. This molecule is now known as murine IL6. As part of the characterization of murine Il-6, genomic sequences have been localized to the proximal end of mouse chromosome 5 via Southern analysis of restriction fragment length polymorphisms. The removal of IL6 from IL6-dependent PCT cell lines results in a growth arrest in early G1. This is accompanied by a rapid and specific loss of transferrin receptor expression and results in eventual cell death. It appears that the response to IL6 is at least partially dependent on Ca++ because functional Ca++ channels are necessary for the PCT cells to pass through G1 and to maintain transferrin receptor expression.
Animals↗
Receptors for Fc epsilon and Fc gamma are linked on mouse chromosome 1.
Recently isolated cDNA clones for the high affinity Fc epsilon receptors on mast cells and basophils (Fc epsilon RI alpha) and Fc gamma receptors on macrophages and lymphocytes (Fc gamma 2b/gamma 1R) are homologous members of the Ig supergene family. Analysis of the segregation of restriction fragment length polymorphism in crosses of inbred mice now establish that the structural genes encoding both Fc epsilon RI alpha and Fc gamma 2b/gamma 1R are indeed discrete genes and are linked at the distal end of mouse chromosome 1. This finding raises the possibility that a family of Fc receptors could be found in a region that is known to contain immunologically important markers of lymphocyte surface Ag and autoimmune defects.
Animals↗
Organization of the distal end of mouse chromosome 4.
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Animals↗
Mapping of the Ly-4 (L3T4) T-cell differentiation antigen on mouse chromosome 6 by the use of RFLPs in an interspecific cross.
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Animals↗
T-cell receptor VT beta genes in natural populations of mice.
The composition of 15 VT beta gene subfamilies has been examined by Southern hybridization among a broad spectrum of colony bred rat and mouse species extending phylogenetically from Rattus to Mus musculus domesticus. Most mouse species contain a similar content of VT beta genes as determined by the number of hybridizing restriction fragment (RF) bands. Furthermore, the extent of restriction fragment length polymorphism (RFLP) appears to be limited. Some VT beta gene families, however, are missing from Rattus (VT beta 7, VT beta 12) and M. shortridgei (VT beta 9, VT beta 16). Extension of the VT beta survey to a panel of 38 wild caught mice reveals that nearly a third lack specific hybridization to the VT beta 5 probe. Previous reports have established that the mouse inbred strains SJL, C57BR, C57L, and SWR lack 50% of their VT beta repertoire, including VT beta 5 (Behlke et al. 1985). This study demonstrates that natural populations of mice also carry a significantly reduced VT beta gene repertoire.
Animals↗
Hormonal modulation of sex differences in resistance to Leishmania major systemic infections.
Differences in susceptibility to intravenously inoculated Leishmania major were observed in male and female mice of the BALB/cAnPt, DBA/2N, and DBA/2J strains and (BALB/cAnPt x DBA/2N)F1 hybrids. In all cases, males had significantly higher liver parasite burdens than females. Orchidectomy of BALB/c males resulted in a 20% decrease in the number of parasites in the liver compared with either normal or sham-gonadectomized controls. Additionally, testosterone treatment of female BALB/c mice resulted in an 88% increase in the number of liver amastigotes. These results suggest that the hormone testosterone can modulate systemic L. major infections in BALB/c mice.
Animals↗
Mapping of the bcl-2 oncogene on mouse chromosome 1.
Two bcl-2 alleles have been identified in inbred strains of mice by restriction fragment length polymorphism (RFLP). Analysis of a bcl-2 RFLP in a series of bilineal congenic strains (C.D2), developed as a tool for chromosomal mapping studies, revealed linkage of bcl-2 to the Idh-1/Pep-3 region of murine chromosome 1. The co-segregation of bcl-2 alleles with allelic forms of two other chromosome 1 loci, Ren-1,2 and Spna-1, in a set of back-cross progeny, positions bcl-2 7.8 cM centromeric from Ren-1,2.
Animals↗
Mouse lymphotoxin and tumor necrosis factor: structural analysis of the cloned genes, physical linkage, and chromosomal position.
Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytotoxic and immunoregulatory lymphokines which have similar activities but are produced by different cell types. We have cloned the murine LT and TNF genes from a lambda:mouse DNA recombinant library, using as probes synthetic oligonucleotides defined by portions of the human LT or TNF cDNA sequences. Analysis of the genomic clones indicates that the LT and TNF genes are physically linked, i.e., approximately 1.2 kb separates the 3' end of LT from the 5' end of TNF genes. By using, first, a series of recombinant inbred lines, and second, a series of H-2-recombinant congenic strains, we determined that the LT/TNF gene cluster lies on chromosome 17, closely linked to the H-2D end of the murine H-2 complex. Comparison of the primary sequence of murine and human LT revealed that the intron-exon structure of murine LT is similar in these two species. Comparison of the predicted amino acid sequences of murine and human LT indicates that the proteins are about 72% homologous with much greater sequence conservation in regions encoding the COOH-terminal portion. Comparison of the 5' flanking sequence of LT to a number of genes that are specifically expressed in activated T cells reveals a number of conserved sequences that may play a role in control of these genes.
Amino Acid Sequence↗