Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

Peter Chen; Simon Bélanger; Oscar A. Aguilar; Qiang Zhang; Aaron St.-Laurent; M. Munir Ahmad Rahim; Andrew P. Makrigiannis; James R. Carlyle

doi:10.1007/s00251-011-0542-8

Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

Peter Chen, Simon Bélanger, Oscar A. Aguilar, Qiang Zhang, Aaron St.-Laurent, M. Munir Ahmad Rahim, Andrew P. Makrigiannis, James R. Carlyle

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

26 Citas (Scopus)

Resumen

The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

Idioma original	English
Páginas (desde-hasta)	627-640
Número de páginas	14
Publicación	Immunogenetics
Volumen	63
N.º	10
DOI	https://doi.org/10.1007/s00251-011-0542-8
Estado	Published - oct. 2011
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
Acknowledgments We thank Stephen Anderson for assistance with analyzing BAC clones, Lise Kveberg and John Vaage for providing BALB-strain Clr expression constructs, and Colin Brooks for providing a B6 Clrx cDNA vector. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR MOP 86630; to A.P.M. & J.R.C), and an early researcher award from the Ontario Ministry of Research and Innovation (to J.R. C). P.C. was supported by an Ontario Graduate Scholarship. S.B. is supported by a Fonds de la recherche en santé Québec scholarship. A. P.M. is the Canada research chair in Innate Pathogen Resistance. J.R.C. holds a CIHR new investigator award and an investigator in the pathogenesis of infectious disease award from the Burroughs Wellcome Fund, USA. The authors have no conflicting financial interests.

ASJC Scopus Subject Areas

Immunology
Genetics

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1007/s00251-011-0542-8

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Chen, P., Bélanger, S., Aguilar, O. A., Zhang, Q., St.-Laurent, A., Rahim, M. M. A., Makrigiannis, A. P., & Carlyle, J. R. (2011). Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism. Immunogenetics, 63(10), 627-640. https://doi.org/10.1007/s00251-011-0542-8

Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism. / Chen, Peter; Bélanger, Simon; Aguilar, Oscar A. et al.
En: Immunogenetics, Vol. 63, N.º 10, 10.2011, p. 627-640.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

Chen, P, Bélanger, S, Aguilar, OA, Zhang, Q, St.-Laurent, A, Rahim, MMA, Makrigiannis, AP & Carlyle, JR 2011, 'Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism', Immunogenetics, vol. 63, n.º 10, pp. 627-640. https://doi.org/10.1007/s00251-011-0542-8

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title = "Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism",

abstract = "The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.",

author = "Peter Chen and Simon B{\'e}langer and Aguilar, {Oscar A.} and Qiang Zhang and Aaron St.-Laurent and Rahim, {M. Munir Ahmad} and Makrigiannis, {Andrew P.} and Carlyle, {James R.}",

note = "Funding Information: Acknowledgments We thank Stephen Anderson for assistance with analyzing BAC clones, Lise Kveberg and John Vaage for providing BALB-strain Clr expression constructs, and Colin Brooks for providing a B6 Clrx cDNA vector. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR MOP 86630; to A.P.M. & J.R.C), and an early researcher award from the Ontario Ministry of Research and Innovation (to J.R. C). P.C. was supported by an Ontario Graduate Scholarship. S.B. is supported by a Fonds de la recherche en sant{\'e} Qu{\'e}bec scholarship. A. P.M. is the Canada research chair in Innate Pathogen Resistance. J.R.C. holds a CIHR new investigator award and an investigator in the pathogenesis of infectious disease award from the Burroughs Wellcome Fund, USA. The authors have no conflicting financial interests.",

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AU - Rahim, M. Munir Ahmad

AU - Makrigiannis, Andrew P.

AU - Carlyle, James R.

N1 - Funding Information: Acknowledgments We thank Stephen Anderson for assistance with analyzing BAC clones, Lise Kveberg and John Vaage for providing BALB-strain Clr expression constructs, and Colin Brooks for providing a B6 Clrx cDNA vector. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR MOP 86630; to A.P.M. & J.R.C), and an early researcher award from the Ontario Ministry of Research and Innovation (to J.R. C). P.C. was supported by an Ontario Graduate Scholarship. S.B. is supported by a Fonds de la recherche en santé Québec scholarship. A. P.M. is the Canada research chair in Innate Pathogen Resistance. J.R.C. holds a CIHR new investigator award and an investigator in the pathogenesis of infectious disease award from the Burroughs Wellcome Fund, USA. The authors have no conflicting financial interests.

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N2 - The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

AB - The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

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Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

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ASJC Scopus Subject Areas

PubMed: MeSH publication types

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