The major locus for mouse adenovirus susceptibility maps to genes of the hematopoietic cell surface-expressed LY6 family

Katherine R. Spindler, Amanda R. Welton, Efrem Lim, Suman Duvvuru, Irene W. Althaus, Jennifer E. Imperiale, Adam I. Daoud, Elissa J. Chesler

Research output: Contribution to journalArticle

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Abstract

Susceptibility to mouse adenovirus type 1 is associated with the major quantitative trait locus Msq1. Msq1 was originally mapped to a 13-Mb region of mouse chromosome (Chr) 15 in crosses between SJL/J and BALB/cJ inbred mice. We have now narrowed Msq1 to a 0.75-Mb interval from 74.68 to 75.43 Mb, defined by two anonymous markers, rs8259436 and D15Spn14, using data from 1396 backcross mice. The critical interval includes 14 Ly6 or Ly6-related genes, including Ly6a (encoding Sca-1/TAP), Ly6e (Sca-2/Tsa1), Ly6g (Gr-1), and gpihbp1 (GPI-anchored high-density lipoprotein-binding protein 1), as well as the gene encoding an aldosterone synthase (Cyp11b2). The Ly6 family members are attractive candidates for virus susceptibility genes because their products are GPI-anchored membrane proteins expressed on lymphoid and myeloid cells, with proposed functions in cell adhesion and cell signaling. To determine interstrain variation in susceptibility and produce additional resources for cloning Msq1, we assayed the susceptibility phenotype of four previously untested inbred mouse strains. Susceptibility of strain 129S6/SvEvTac was subsequently localized to the Ly6 complex region, using polymorphic genetic markers on Chr 15 in a population of 271 (129S6/ SvEvTac x BALB/cJ)F1 x BALB/cJ backcross mice. We identified a major 129S6/SvEvTac susceptibility allele, Msq1129S6, on Chr 15 in the same region as Msq1SJL. The results indicate that a major host factor in mouse adenovirus type 1 susceptibility is likely to be a member of the Ly6 gene family.

Original languageEnglish (US)
Pages (from-to)3055-3062
Number of pages8
JournalJournal of Immunology
Volume184
Issue number6
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

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Adenoviridae
Chromosomes, Human, Pair 15
Genes
Cytochrome P-450 CYP11B2
Inbred Strains Mice
Quantitative Trait Loci
Myeloid Cells
Genetic Markers
Cell Adhesion
Organism Cloning
Membrane Proteins
Alleles
Lymphocytes
Viruses
Phenotype
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Spindler, K. R., Welton, A. R., Lim, E., Duvvuru, S., Althaus, I. W., Imperiale, J. E., ... Chesler, E. J. (2010). The major locus for mouse adenovirus susceptibility maps to genes of the hematopoietic cell surface-expressed LY6 family. Journal of Immunology, 184(6), 3055-3062. https://doi.org/10.4049/jimmunol.0903363

The major locus for mouse adenovirus susceptibility maps to genes of the hematopoietic cell surface-expressed LY6 family. / Spindler, Katherine R.; Welton, Amanda R.; Lim, Efrem; Duvvuru, Suman; Althaus, Irene W.; Imperiale, Jennifer E.; Daoud, Adam I.; Chesler, Elissa J.

In: Journal of Immunology, Vol. 184, No. 6, 15.03.2010, p. 3055-3062.

Research output: Contribution to journalArticle

Spindler, KR, Welton, AR, Lim, E, Duvvuru, S, Althaus, IW, Imperiale, JE, Daoud, AI & Chesler, EJ 2010, 'The major locus for mouse adenovirus susceptibility maps to genes of the hematopoietic cell surface-expressed LY6 family', Journal of Immunology, vol. 184, no. 6, pp. 3055-3062. https://doi.org/10.4049/jimmunol.0903363
Spindler, Katherine R. ; Welton, Amanda R. ; Lim, Efrem ; Duvvuru, Suman ; Althaus, Irene W. ; Imperiale, Jennifer E. ; Daoud, Adam I. ; Chesler, Elissa J. / The major locus for mouse adenovirus susceptibility maps to genes of the hematopoietic cell surface-expressed LY6 family. In: Journal of Immunology. 2010 ; Vol. 184, No. 6. pp. 3055-3062.
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abstract = "Susceptibility to mouse adenovirus type 1 is associated with the major quantitative trait locus Msq1. Msq1 was originally mapped to a 13-Mb region of mouse chromosome (Chr) 15 in crosses between SJL/J and BALB/cJ inbred mice. We have now narrowed Msq1 to a 0.75-Mb interval from 74.68 to 75.43 Mb, defined by two anonymous markers, rs8259436 and D15Spn14, using data from 1396 backcross mice. The critical interval includes 14 Ly6 or Ly6-related genes, including Ly6a (encoding Sca-1/TAP), Ly6e (Sca-2/Tsa1), Ly6g (Gr-1), and gpihbp1 (GPI-anchored high-density lipoprotein-binding protein 1), as well as the gene encoding an aldosterone synthase (Cyp11b2). The Ly6 family members are attractive candidates for virus susceptibility genes because their products are GPI-anchored membrane proteins expressed on lymphoid and myeloid cells, with proposed functions in cell adhesion and cell signaling. To determine interstrain variation in susceptibility and produce additional resources for cloning Msq1, we assayed the susceptibility phenotype of four previously untested inbred mouse strains. Susceptibility of strain 129S6/SvEvTac was subsequently localized to the Ly6 complex region, using polymorphic genetic markers on Chr 15 in a population of 271 (129S6/ SvEvTac x BALB/cJ)F1 x BALB/cJ backcross mice. We identified a major 129S6/SvEvTac susceptibility allele, Msq1129S6, on Chr 15 in the same region as Msq1SJL. The results indicate that a major host factor in mouse adenovirus type 1 susceptibility is likely to be a member of the Ly6 gene family.",
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