The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Thomas R. King - One of the best experts on this subject based on the ideXlab platform.
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The male sterility and Histoincompatibility (mshi) mutation in mice is a natural variant of microtubule-associated protein 7 (Mtap7).
Molecular genetics and metabolism, 2009Co-Authors: David R. Magnan, Damek V Spacek, Thomas R. KingAbstract:Abstract Males homozygous for the mouse male sterility and Histoincompatibility ( mshi ) mutation exhibit small testes and produce no sperm. In addition, mshi generates an "antigen-loss" Histoincompatibility barrier, such that homozygous mutants reject skin grafts from wild type co-isogenic BALB/cByJ donors. To facilitate the molecular characterization of the pleiotropic mshi mutation, we genetically mapped mshi into a 0.68 megabasepair region which contains fewer than 10 candidate genes. Complementation testing showed that one of these, Mtap7 , is disrupted in mshi mice. Sequence analysis has revealed a 13 kilobasepair deletion in BALB/cByJ- mshi /J mice that begins in Intron 10–11 of Mtap7 , and ends less than 2000 base pairs downstream of the wild type gene. Analysis of the mutant cDNA predicts that Mtap7 mshi encodes a 457 amino acid protein, the first 423 of which are identical to wild type, and the last 34 of which are due to aberrant mRNA splicing with two cryptic exons in the Mtap7 to P04Rik intergenic region. This molecular assignment for the mshi mutation further supports an essential role for microtubule stabilization in spermatogenesis and indicates a new role in allograft transplantation.
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mouse male sterility and Histoincompatibility mshi maps between the d10mit51 168 212 cluster and d10mit213
Mammalian Genome, 1999Co-Authors: Michael C. Rule, Kenute A. Myrie, Raye J. Mutcherson, Andrew D. Foss, Tien K.-x. Nguyen, Thomas R. KingAbstract:The recessive male sterility and Histoincompatibility (mshi) mutation in the mouse generates pleiotropic effects on graft transplantation and male reproduction. Previous analysis of backcross mice typed for mshi either by testicular morphology or by allograft rejection has located each trait to a 20-cM region on proximal mouse Chr 10. Here we present the microsatellite polymorphism analysis of a new 276-member intraspecific backcross panel—including a set of 135 males typed for sterility and Histoincompatibility—that places both features controlled by mshi within a 1.7-cM interval between markers D10Mit51/168/212 and D10Mit213. In addition, this analysis has allowed an explicit test of a two-gene model for the mshi locus and has provided a measurement of the penetrance of the mshi-generated histogenic phenotype in both male (88.4 ± 3.9%) and female (91.0 ± 3.5%) mutants. The fine-structure map presented should facilitate a chromosome walk across this region and, ultimately, the molecular identification of the gene or genes affected by this interesting mutation.
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Mouse male sterility and Histoincompatibility (mshi) maps between the D10Mit51/168/212 cluster and D10Mit213.
Mammalian genome : official journal of the International Mammalian Genome Society, 1999Co-Authors: Michael C. Rule, Kenute A. Myrie, Raye J. Mutcherson, Andrew D. Foss, Tien K.-x. Nguyen, Thomas R. KingAbstract:The recessive male sterility and Histoincompatibility (mshi) mutation in the mouse generates pleiotropic effects on graft transplantation and male reproduction. Previous analysis of backcross mice typed for mshi either by testicular morphology or by allograft rejection has located each trait to a 20-cM region on proximal mouse Chr 10. Here we present the microsatellite polymorphism analysis of a new 276-member intraspecific backcross panel—including a set of 135 males typed for sterility and Histoincompatibility—that places both features controlled by mshi within a 1.7-cM interval between markers D10Mit51/168/212 and D10Mit213. In addition, this analysis has allowed an explicit test of a two-gene model for the mshi locus and has provided a measurement of the penetrance of the mshi-generated histogenic phenotype in both male (88.4 ± 3.9%) and female (91.0 ± 3.5%) mutants. The fine-structure map presented should facilitate a chromosome walk across this region and, ultimately, the molecular identification of the gene or genes affected by this interesting mutation.
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Molecular Genetic Mapping of the Mouse Male Sterility and Histoincompatibility (mshi) Mutation on Proximal Chromosome 10
Genomics, 1997Co-Authors: Joseph P. Turner, Audrey L. Hildebrandt, Angelene M. Cantwell, Joseph E. Carpentino, Kenute A. Myrie, Thomas R. KingAbstract:The recessive male sterility and Histoincompatibility (mshi) mutation in the mouse generates pleiotropic effects on histocompatibility and male reproduction, while female mutants appear to be reproductively normal. We have mapped the mshi mutation to mouse Chromosome (Chr) 10 by analysis of 126 progeny from an intraspecific backcross. Our analysis both places the male sterility and Histoincompatibility controlled by mshi within a 20-cM interval between the markers D10Mit51/D10Mit212 and D10Mit170 and has allowed the ordering of several other microsatellite markers on Chr 10 that were previously unresolved. The high-resolution backcross panel we describe should facilitate the isolation of more tightly linked probe sequences and, ultimately, the molecular identification of the gene or genes affected by this interesting mutation.
M. T. Davisson - One of the best experts on this subject based on the ideXlab platform.
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A new mouse mutation causing male sterility and Histoincompatibility
Mammalian Genome, 1996Co-Authors: P. F. Ward-bailey, K. R. Johnson, M. A. Handel, B. S. Harris, M. T. DavissonAbstract:Male sterility and Histoincompatibility, mshi , is an autosomal recessive mutation in BALB/cBy mice that causes reduced testis size and sterility in homozygous males. The testes of homozygous mutants are highly disorganized and appear to have a block in the regulation of male germ cell proliferation. No heterozygous effect is detectable. Reproduction is unaffected in females carrying the mutation. The mutation also affects histocompatibility; most homozygous males and females reject sex-matched skin grafts from BALB/cBy mice. We used an intercross between BALB/cBy and CAST/Ei to map the mshi mutation to the proximal end of Chromosome (Chr) 10. The most likely gene order places the mutation between D10Mit80 and D10Mit16 , near the interferon gamma receptor locus, Ifgr , which may be a candidate gene for this mutation.
Yoshihiro Komada - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of azithromycin in preventing lethal graft-versus-host disease
Clinical and experimental immunology, 2013Co-Authors: Shotaro Iwamoto, Eiichi Azuma, Tadashi Kumamoto, Masahiro Hirayama, T. Yoshida, Masahiro Ito, Keishirou Amano, Masaru Ido, Yoshihiro KomadaAbstract:Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (BMT) is initiated by donor T lymphocytes that recognize histocompatibility antigens presented by recipient dendritic cells (DCs). Current approaches to reduce GVHD are focused on suppressing donor T lymphocyte responses to alloantigens. However, these strategies may be inadequate in the setting of allogeneic transplants (particularly histoincompatible transplants), may increase the risk of tumour relapse and are associated with high rates of opportunistic infections. We hypothesized that inhibition of recipient DCs might suppress GVHD. We recently demonstrated in vitro that azithromycin, a macrolide antibiotic, also acts as a nuclear factor (NF)-κB inhibitor of murine DCs and inhibits their maturation and functions, including allogeneic responses. We investigated whether azithromycin could prevent alloreactions in a murine Histoincompatibility model. Oral administration of azithromycin to recipient mice for 5 days during major-histoincompatible BMT suppressed lethal GVHD significantly, whereas ex-vivo lymphocyte function was not affected by the drug. These data suggest that azithromycin has potential as a novel prophylactic drug for lethal GVHD.
Sebastian Joyce - One of the best experts on this subject based on the ideXlab platform.
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Minor histocompatibility antigens: presentation principles, recognition logic and the potential for a healing hand.
Current opinion in organ transplantation, 2010Co-Authors: Charles T. Spencer, Pavlo Gilchuk, Srdjan Dragovic, Sebastian JoyceAbstract:There is ample evidence indicating a pathologic role for minor histocompatibility antigens in inciting graft-versus-host disease in major histocompatibility complex (MHC)-matched bone marrow transplantation and rejection of solid organ allografts. Here we review the current knowledge of the genetic and biochemical bases for the cause of minor Histoincompatibility and the structural basis for the recognition of the resulting alloantigens by the T-cell receptor. Recent evidence indicates that we as independently conceived individuals are genetically unique, thus, offering a mechanism for minor Histoincompatibility between MHC-identical donor-recipient pairs. Furthermore, advances in delineating the mechanisms underlying antigen cross-presentation by MHC class I molecules and a critical role for autophagy in presenting cytoplasmic antigens by MHC class II molecules have been made. These new insights coupled with the X-ray crystallographic solution of several peptide/MHC-T-cell receptor structures have revealed mechanisms of Histoincompatibility. On the basis of these new insights, ways to test for allograft compatibility and concoction of immunotherapies are discussed.
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Minor histocompatibility antigens: presentation principles, recognition logic and the potential for a healing hand.
Current opinion in organ transplantation, 2010Co-Authors: Charles T. Spencer, Pavlo Gilchuk, Srdjan Dragovic, Sebastian JoyceAbstract:PURPOSE OF REVIEW There is ample evidence indicating a pathologic role for minor histocompatibility antigens in inciting graft-versus-host disease in major histocompatibility complex (MHC)-matched bone marrow transplantation and rejection of solid organ allografts. Here we review the current knowledge of the genetic and biochemical bases for the cause of minor Histoincompatibility and the structural basis for the recognition of the resulting alloantigens by the T-cell receptor. RECENT FINDINGS Recent evidence indicates that we as independently conceived individuals are genetically unique, thus, offering a mechanism for minor Histoincompatibility between MHC-identical donor-recipient pairs. Furthermore, advances in delineating the mechanisms underlying antigen cross-presentation by MHC class I molecules and a critical role for autophagy in presenting cytoplasmic antigens by MHC class II molecules have been made. These new insights coupled with the X-ray crystallographic solution of several peptide/MHC-T-cell receptor structures have revealed mechanisms of Histoincompatibility. SUMMARY On the basis of these new insights, ways to test for allograft compatibility and concoction of immunotherapies are discussed.
P. F. Ward-bailey - One of the best experts on this subject based on the ideXlab platform.
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A new mouse mutation causing male sterility and Histoincompatibility
Mammalian Genome, 1996Co-Authors: P. F. Ward-bailey, K. R. Johnson, M. A. Handel, B. S. Harris, M. T. DavissonAbstract:Male sterility and Histoincompatibility, mshi , is an autosomal recessive mutation in BALB/cBy mice that causes reduced testis size and sterility in homozygous males. The testes of homozygous mutants are highly disorganized and appear to have a block in the regulation of male germ cell proliferation. No heterozygous effect is detectable. Reproduction is unaffected in females carrying the mutation. The mutation also affects histocompatibility; most homozygous males and females reject sex-matched skin grafts from BALB/cBy mice. We used an intercross between BALB/cBy and CAST/Ei to map the mshi mutation to the proximal end of Chromosome (Chr) 10. The most likely gene order places the mutation between D10Mit80 and D10Mit16 , near the interferon gamma receptor locus, Ifgr , which may be a candidate gene for this mutation.