Genetic structure and chromosomal mapping of MyD88.

The myeloid differentiation (MyD) marker MyD88 was initially characterized as a primary response gene, upregulated in mouse M1 myeloleukemic cells in response to differentiation induced by interleukin-6. Subsequent analysis revealed that MyD88 possesses a unique modular structure, which consists of an N-terminal "death domain," similar to the intracellular segments of TNF receptor 1 and Fas, and a C-terminal region related to the cytoplasmic domains of the Drosophila morphogen Toll and vertebrate interleukin-1 receptors. In this report we describe the cloning and gene structure of mouse MyD88. The complete coding sequence of mouse MyD88 spans five exons, with the first exon encoding the complete death domain. Zooblot analysis revealed that MyD88 is an evolutionarily conserved gene. MyD88 was localized to the distal region of mouse chromosome 9 by interspecific backcross mapping. The human homolog (hMyD88) was mapped to chromosome 3p22-p21.3 by PCR analysis of a human chromosome 3 somatic cell hybrid mapping panel. Northern blot analysis revealed widespread expression of MyD88 in many adult mouse tissues, and RT-PCR studies detected MyD88 mRNA in T and B cell lines and differentiating embryonic stem cells. The broad expression pattern demonstrates that mouse MyD88 expression is not restricted to cells of myeloid lineage as was originally believed.

[1]  G. Hardiman,et al.  Molecular characterization and modular analysis of human MyD88. , 1996, Oncogene.

[2]  S. Naylor,et al.  An 80 Kb P1 clone from chromosome 3p21.3 suppresses tumor growth in vivo. , 1996, Oncogene.

[3]  Stephen W. Fesik,et al.  NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain , 1996, Nature.

[4]  T. Mcclanahan,et al.  The mouse Wnt-10B gene isolated from helper T cells is widely expressed and a possible oncogene in BR6 mouse mammary tumorigenesis. , 1996, Gene.

[5]  S. Harroch,et al.  5' upstream sequences of MyD88, an IL-6 primary response gene in M1 cells: detection of functional IRF-1 and Stat factors binding sites. , 1995, Nucleic acids research.

[6]  A. Kimchi,et al.  The death domain: a module shared by proteins with diverse cellular functions. , 1995, Trends in biochemical sciences.

[7]  J. Sims,et al.  Genomic organization of the type I and type II IL-1 receptors. , 1995, Cytokine.

[8]  J. Camonis,et al.  Self-association of the Death Domains of the p55 Tumor Necrosis Factor (TNF) Receptor and Fas/APO1 Prompts Signaling for TNF and Fas/APO1 Effects (*) , 1995, The Journal of Biological Chemistry.

[9]  A. Ballabio,et al.  Regional localization of 188 sequence tagged sites on a somatic cell hybrid mapping panel for human chromosome 3. , 1994, Genomics.

[10]  D. Hultmark.  Macrophage differentiation marker MyD88 is a member of the Toll/IL-1 receptor family. , 1994, Biochemical and biophysical research communications.

[11]  J. Sanes,et al.  Interspecific comparisons reveal conserved features of the Drosophila Toll protein. , 1994, Gene.

[12]  L. Glimcher,et al.  Regulation of cytokine gene expression in T helper cell subsets. , 1994, Journal of immunology.

[13]  N. Copeland,et al.  Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6 family with a possible role in T cell development. , 1993, Journal of immunology.

[14]  L. Tartaglia,et al.  A novel domain within the 55 kd TNF receptor signals cell death , 1993, Cell.

[15]  J. Minna,et al.  A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region of tumor suppressor activity. , 1993, Oncogene.

[16]  T. Mcclanahan,et al.  Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells [see comments] , 1993 .

[17]  S. Nagata,et al.  A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. , 1993, The Journal of biological chemistry.

[18]  M. Lerman,et al.  Localization of a novel natural killer triggering receptor locus to human chromosome 3p23-p21 and mouse chromosome 9. , 1993, Genomics.

[19]  K. Arai,et al.  Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells , 1993, Molecular and cellular biology.

[20]  S. Naylor,et al.  Definition of a tumor suppressor locus within human chromosome 3p21-p22. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Wallach,et al.  Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. , 1992, The EMBO journal.

[22]  N. Copeland,et al.  Development and applications of a molecular genetic linkage map of the mouse genome. , 1991, Trends in genetics : TIG.

[23]  D. Liebermann,et al.  Dissection of the immediate early response of myeloid leukemia cells to terminal differentiation and growth inhibitory stimuli. , 1990, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[24]  D. Liebermann,et al.  Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6. , 1990, Oncogene.

[25]  D. Liebermann,et al.  Complexity of the immediate early response of myeloid cells to terminal differentiation and growth arrest includes ICAM-1, Jun-B and histone variants. , 1990, Oncogene.

[26]  M. Everson,et al.  Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells. , 1989, Blood.

[27]  D. Liebermann,et al.  Proto-oncogene expression and dissection of the myeloid growth to differentiation developmental cascade. , 1989, Oncogene.

[28]  C. Chiu,et al.  IL-6 is a differentiation factor for M1 and WEHI-3B myeloid leukemic cells. , 1989, Journal of immunology.

[29]  D. Rennick,et al.  IL-3 and stromal cell-derived factor synergistically stimulate the growth of pre-B cell lines cloned from long-term lymphoid bone marrow cultures. , 1989, Journal of immunology.

[30]  J. Osinga,et al.  Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer , 1987, Nature.

[31]  O. Witte,et al.  A single bone marrow-derived stromal cell type supports the in vitro growth of early lymphoid and myeloid cells , 1987, Cell.

[32]  C. Uyttenhove,et al.  Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[33]  K. J. Kim,et al.  Con A induction of IgG secretion from a B-lymphoid tumour cell line, A20. , 1986, Immunology.

[34]  L. Arnold,et al.  Antigen-induced lymphomagenesis: identification of a murine B cell lymphoma with known antigen specificity. , 1983, Journal of immunology.

[35]  N. Copeland,et al.  Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus , 1982, Journal of virology.

[36]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[37]  J. Watson.  Continuous proliferation of murine antigen-specific helper T lymphocytes in culture , 1979, The Journal of experimental medicine.

[38]  P. O'Connell,et al.  Mapping 638 STSs to regions of human chromosome 3. , 1996, Cytogenetics and cell genetics.

[39]  J. Xiong,et al.  Sequence, genomic organization, and chromosome localization of the mouse TRADD gene. , 1995, Journal of inflammation.

[40]  J. Minna,et al.  Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer , 1987, Nature.

[41]  C. Janeway,et al.  Induction of receptors for interleukin 2 requires T cell Ag:Ia receptor crosslinking and interleukin 1. , 1984, Lymphokine research.

[42]  E. L. Green.  Linkage, recombination and mapping , 1981 .

[43]  E. L. Green.  Genetics and probability in animal breeding experiments. , 1981 .