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Lyst  -  lysosomal trafficking regulator

Mus musculus

Synonyms: Beige protein, Bg, CHS1 homolog, Chs1, D13Sfk13, ...
 
 
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Disease relevance of Lyst

  • The murine beige mutant phenotype and the human Chediak-Higashi syndrome are caused by mutations in the murine Lyst (lysosomal trafficking regulator) gene and the human CHS gene, respectively [1].
  • We have compared the susceptibility of bg/bg and bg/+ C57BL/6J mice to infection with murine cytomegalovirus (MCMV) [2].
  • Tumor spheroids of the human rhabdomyosarcoma cell line A673, with a diameter between 600 and 1000 microns, were implanted in dorsal skinfold chambers inserted on Beige nude/xid mice [3].
  • Experimental infection of immunodeficient NIH-3 (N:NIH-bg-nu-xid) mice with Borrelia burgdorferi was found to result in multisystem histopathologic lesions [4].
  • Interferon alpha/beta (IFN alpha/beta) is highly effective in inhibiting the development of Friend erythroleukemia cell (FLC) visceral metastases in DBA/2 mice injected intravenously (i.v.) with FLC, but does not protect FLC-injected DBA/2 beige (bg/bg) mice [5].
 

Psychiatry related information on Lyst

  • BACKGROUND: Chediak-Higashi syndrome (CHS) is a systemic disorder of human and mouse (beige, bg) that is characterized by aberrant intracellular protein kinesis and lysosomal trafficking [6].
  • However, SCID-bg mice always showed the smallest within-group variance (individual difference) in the serum guinea pig IgG concentrations (P < 0.05, versus C.B.-17-scid-AGM1 mice at 1, 2, and 3 weeks and versus C.B.-17-scid mice at 2 weeks) [7].
 

High impact information on Lyst

 

Biological context of Lyst

  • The physical and genetic map surrounding the Lyst gene on mouse chromosome 13 [10].
  • Grey, a novel mutation in the murine Lyst gene, causes the beige phenotype by skipping of exon 25 [1].
  • Test crosses with beige homozygous mutant mice (Lyst(bg)) showed that double heterozygotes (Lyst(bg)/Lyst(bg-grey)) were phenotypically indistinguishable from either homozygous parent, demonstrating that the ENU mutation was an allele of the murine Lyst gene [1].
  • Analysis of the genomic Lyst locus around exon 25 showed that the splice donor at the end of exon 25 showed a T-to-C transition point mutation [1].
  • A molecular genetic linkage map of mouse chromosome 13 anchored by the beige (bg) and satin (sa) loci [11].
 

Anatomical context of Lyst

  • Defective trafficking of cytoplasmic granules caused by the Lyst mutation also resulted in loss of antitumor activity of the dipeptide [12].
  • In vivo activation of NK cells in bg and control mice resulted in a decrease in tumour growth rate and metastatic frequency [13].
  • CHS and bg cells have giant, perinuclear vesicles with characteristics of late endosomes and lysosomes that arise from dysregulated homotypic fusion [9].
  • Beige mice are more susceptible to lethal infection and develop 33- to 43-fold higher virus titers in the liver, spleen, and kidney than do bg/+ mice after a sublethal infection, although virus replication is the same in vitro in cultured fibroblasts or epithelial cells from these mice [2].
  • Cultured mouse fibroblasts in which the Beige protein was overexpressed had smaller than normal lysosomes that were more peripherally distributed than in control cells [14].
 

Associations of Lyst with chemical compounds

  • We prepared a polyclonal antiserum against a glutathione S-transferase-Beige fusion protein and demonstrated by Western analysis that the beige gene encodes a protein of 400 kDa that is expressed in cultured murine fibroblasts as well as most mouse tissues [14].
  • The KSN-xid and KSN-BNX mice had a reduced percentage of B220-positive cells in the spleen compared with KSN and KSN-bg mice, but they had increased percentages of Thy-1 and asialo GM1-positive cells [15].
  • MATERIALS AND METHODS: Androgen-sensitive LNCaP or -insensitive PC-3 human prostate carcinoma cells were injected directly into the femur medullas of male nude Beige mice, the animals were then sacrificed at successive time intervals to study the gross and microscopic characteristics of the established tumors [16].
  • BPH fragments prepared from fresh surgical specimens were implanted subcutaneously (s.c.), intraperitoneally (i.p.), or under the renal capsules (r.c.) into male Beige nude mice, which had been implanted s.c. with a Silastic tube filled with 4-dihydrotestosterone (DHT) or cholesterol [17].
 

Regulatory relationships of Lyst

  • We introduced two mutant genes (beige; bg that induces the deficiency of natural killer (NK) activity and xid that decreases the production of immunoglobulin) into KSN nude mice with high reproductive performances [18].
 

Other interactions of Lyst

  • Two of these loci, Nid and Estm9, are genes and represent candidates for bg [6].
  • Progeny from one intra- and two inter-specific backcrosses between divergent strains of mice were typed to map multiple markers in relation to two pigment mutations on mouse chromosome 13, beige (bg) and pearl (pe) [19].
  • This data confirms results of prior chromosomal mapping studies utilizing bg as an anchor locus, and provides previously unreported information defining the localization of the prolactin gene on mouse chromosome 13 [19].
  • Because HlS is closely linked to the dominant visible marker extra toes (Xt), Tcrg must be within 5 cM of the beige (bg) locus [20].
  • METHODS: Four mouse pigmentation phenotypes were used: fully pigmented, albino, Beige, and Himalayan [21].
 

Analytical, diagnostic and therapeutic context of Lyst

  • The bg mutation in mice is an animal model for humans with Chediak-Higashi syndrome; we speculate that the human gamma-chain may be closely linked to the human mutation and may be a useful diagnostic tool [20].
  • SCID-bg mice as xenograft recipients [7].
  • Throughout the experimental period (1, 2, and 3 weeks after transplantation), the average serum guinea pig IgG concentrations was highest in C.B.-17-scid-AGM1 mice followed by SCID-bg mice and lowest in C.B.-17-scid mice without antiserum treatment, though we could not find any statistical significance among these groups [7].
  • We developed a passive immunization model in SCID/Beige mice to assess the effect of human and mouse anti-adenovirus antibodies on systemic administration of a rAd vector expressing beta-galactosidase (rAd-betagal) [22].
  • The principal morphological expression of the bg phenotype in RPM is the presence of elongated dumbbell-shaped, horseshoe-shaped, and ring-formed cytoplasmic lysosomes demonstrable by electron microscopy [23].

References

  1. Grey, a novel mutation in the murine Lyst gene, causes the beige phenotype by skipping of exon 25. Runkel, F., Büssow, H., Seburn, K.L., Cox, G.A., Ward, D.M., Kaplan, J., Franz, T. Mamm. Genome (2006) [Pubmed]
  2. Increased susceptibility to cytomegalovirus infection in beige mutant mice. Shellam, G.R., Allan, J.E., Papadimitriou, J.M., Bancroft, G.J. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  3. Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Borgström, P., Hillan, K.J., Sriramarao, P., Ferrara, N. Cancer Res. (1996) [Pubmed]
  4. The NIH-3 immunodeficient mouse is a model for Lyme borreliosis myositis and carditis. Defosse, D.L., Duray, P.H., Johnson, R.C. Am. J. Pathol. (1992) [Pubmed]
  5. Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN alpha/beta therapy of Friend erythroleukemia visceral metastases. Kaido, T., Gresser, I., Maury, C., Maunoury, M.T., Vignaux, F., Belardelli, F. Int. J. Cancer (1993) [Pubmed]
  6. Positional cloning of the Chediak-Higashi syndrome gene: genetic mapping of the beige locus on mouse chromosome 13. Kingsmore, S.F., Barbosa, M.D., Tchernev, V.T., Detter, J.C., Lossie, A.C., Seldin, M.F., Holcombe, R.F. J. Investig. Med. (1996) [Pubmed]
  7. SCID-bg mice as xenograft recipients. Shibata, S., Asano, T., Ogura, A., Hashimoto, N., Hayakawa, J., Uetsuka, K., Nakayama, H., Doi, K. Lab. Anim. (1997) [Pubmed]
  8. Identification of the murine beige gene by YAC complementation and positional cloning. Perou, C.M., Moore, K.J., Nagle, D.L., Misumi, D.J., Woolf, E.A., McGrail, S.H., Holmgren, L., Brody, T.H., Dussault, B.J., Monroe, C.A., Duyk, G.M., Pryor, R.J., Li, L., Justice, M.J., Kaplan, J. Nat. Genet. (1996) [Pubmed]
  9. Identification of the homologous beige and Chediak-Higashi syndrome genes. Barbosa, M.D., Nguyen, Q.A., Tchernev, V.T., Ashley, J.A., Detter, J.C., Blaydes, S.M., Brandt, S.J., Chotai, D., Hodgman, C., Solari, R.C., Lovett, M., Kingsmore, S.F. Nature (1996) [Pubmed]
  10. The physical and genetic map surrounding the Lyst gene on mouse chromosome 13. Misumi, D.J., Nagle, D.L., McGrail, S.H., Dussault, B.J., Smutko, J.S., Chen, H., Charlat, O., Duyk, G.M., Ebeling, C., Baldini, L., Carlson, G.A., Moore, K.J. Genomics (1997) [Pubmed]
  11. A molecular genetic linkage map of mouse chromosome 13 anchored by the beige (bg) and satin (sa) loci. Justice, M.J., Silan, C.M., Ceci, J.D., Buchberg, A.M., Copeland, N.G., Jenkins, N.A. Genomics (1990) [Pubmed]
  12. Natural killer cell cytolytic activity is necessary for in vivo antitumor activity of the dipeptide L-glutamyl-L-tryptophan. Smith, D.L., Cai, J., Zhu, S., Wei, W., Fukumoto, J., Sharma, S., Masood, R., Gill, P.S. Int. J. Cancer (2003) [Pubmed]
  13. Role of NK cells in tumour growth and metastasis in beige mice. Talmadge, J.E., Meyers, K.M., Prieur, D.J., Starkey, J.R. Nature (1980) [Pubmed]
  14. The Beige/Chediak-Higashi syndrome gene encodes a widely expressed cytosolic protein. Perou, C.M., Leslie, J.D., Green, W., Li, L., Ward, D.M., Kaplan, J. J. Biol. Chem. (1997) [Pubmed]
  15. New immunodeficient mouse strains bred by introducing beige and xid mutations into the KSN nude strain. Ishigaki, Y., Hayakawa, J., Hashimoto, N., Nikaido, H., Nikaido, O. Lab. Anim. Sci. (1996) [Pubmed]
  16. Comparative intraosseal growth of human prostate cancer cell lines LNCaP and PC-3 in the nude mouse. Soos, G., Jones, R.F., Haas, G.P., Wang, C.Y. Anticancer Res. (1997) [Pubmed]
  17. Maintenance of human hyperplastic prostate implants at different sites in athymic mice. Soós, G., Debiec-Rychter, M., Jones, R.F., Zukowski, K., Haas, G.P., Wang, C.Y. Anticancer Res. (1995) [Pubmed]
  18. Enhanced human tumor cell transplantability in a new congenic immunodeficient mouse; KSN-BNX. Ishigaki, Y., Yasuda, K., Hashimoto, N., Nikaido, H., Nikaido, O., Hayakawa, J.I. Folia Microbiol. (Praha) (1998) [Pubmed]
  19. Linkage of loci associated with two pigment mutations on mouse chromosome 13. Holcombe, R.F., Stephenson, D.A., Zweidler, A., Stewart, R.M., Chapman, V.M., Seidman, J.G. Genet. Res. (1991) [Pubmed]
  20. The murine gamma-chain of the T cell receptor is closely linked to a spermatocyte specific histone gene and the beige coat color locus on chromosome 13. Owen, F.L., Taylor, B.A., Zweidler, A., Seidman, J.G. J. Immunol. (1986) [Pubmed]
  21. Correlation between rod photoreceptor numbers and levels of ocular pigmentation. Donatien, P., Jeffery, G. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  22. Specific depletion of human anti-adenovirus antibodies facilitates transduction in an in vivo model for systemic gene therapy. Rahman, A., Tsai, V., Goudreau, A., Shinoda, J.Y., Wen, S.F., Ramachandra, M., Ralston, R., Maneval, D., LaFace, D., Shabram, P. Mol. Ther. (2001) [Pubmed]
  23. Qualitative and quantitative differences between resident peritoneal mononuclear phagocytes of beige and control mice. Strausbauch, P., Sehgal, N., Volkman, A. J. Leukoc. Biol. (1984) [Pubmed]
 
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