Genetic basis of tissue specificity of vasculitis in MRL/lpr mice

Akihiro Yamada; Tatsuhiko Miyazaki; Ling Min Lu; Masao Ono; Mitsuko R. Ito; Miho Terada; Shiro Mori; Kazuya Hata; Yoshimi Nozaki; Shuichi Nakatsuru; Yusuke Nakamura; Morikazu Onji; Masato Nose

doi:10.1002/art.10952

Genetic basis of tissue specificity of vasculitis in MRL/lpr mice

Akihiro Yamada, Tatsuhiko Miyazaki, Ling Min Lu, Masao Ono, Mitsuko R. Ito, Miho Terada, Shiro Mori, Kazuya Hata, Yoshimi Nozaki, Shuichi Nakatsuru, Yusuke Nakamura, Morikazu Onji, Masato Nose

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18 Citations (Scopus)

Abstract

Objective. To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp.lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. Methods. Vasculitis in individual MRL/lpr, C3H/ HeJ-lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F₁, and (MRL/lpr × C3H/lpr)F₂ intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F₂ intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. Results. A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of mediumsized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. Conclusion. Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.

Original language	English
Pages (from-to)	1445-1451
Number of pages	7
Journal	Arthritis and Rheumatism
Volume	48
Issue number	5
DOIs	https://doi.org/10.1002/art.10952
Publication status	Published - 2003 May 1

ASJC Scopus subject areas

Immunology and Allergy
Rheumatology
Immunology
Pharmacology (medical)

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10.1002/art.10952

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Genetic basis of tissue specificity of vasculitis in MRL/lpr mice. / Yamada, Akihiro; Miyazaki, Tatsuhiko; Lu, Ling Min; Ono, Masao; Ito, Mitsuko R.; Terada, Miho; Mori, Shiro; Hata, Kazuya; Nozaki, Yoshimi; Nakatsuru, Shuichi; Nakamura, Yusuke; Onji, Morikazu; Nose, Masato.

In: Arthritis and Rheumatism, Vol. 48, No. 5, 01.05.2003, p. 1445-1451.

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title = "Genetic basis of tissue specificity of vasculitis in MRL/lpr mice",

abstract = "Objective. To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp.lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. Methods. Vasculitis in individual MRL/lpr, C3H/ HeJ-lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F1, and (MRL/lpr × C3H/lpr)F2 intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F2 intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. Results. A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of mediumsized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. Conclusion. Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.",

author = "Akihiro Yamada and Tatsuhiko Miyazaki and Lu, {Ling Min} and Masao Ono and Ito, {Mitsuko R.} and Miho Terada and Shiro Mori and Kazuya Hata and Yoshimi Nozaki and Shuichi Nakatsuru and Yusuke Nakamura and Morikazu Onji and Masato Nose",

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AU - Yamada, Akihiro

AU - Miyazaki, Tatsuhiko

AU - Lu, Ling Min

AU - Ono, Masao

AU - Ito, Mitsuko R.

AU - Terada, Miho

AU - Mori, Shiro

AU - Hata, Kazuya

AU - Nozaki, Yoshimi

AU - Nakatsuru, Shuichi

AU - Nakamura, Yusuke

AU - Onji, Morikazu

AU - Nose, Masato

PY - 2003/5/1

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N2 - Objective. To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp.lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. Methods. Vasculitis in individual MRL/lpr, C3H/ HeJ-lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F1, and (MRL/lpr × C3H/lpr)F2 intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F2 intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. Results. A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of mediumsized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. Conclusion. Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.

AB - Objective. To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp.lpr/lpr (MRL/lpr) lupus-prone mice and to identify the susceptibility loci. Methods. Vasculitis in individual MRL/lpr, C3H/ HeJ-lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F1, and (MRL/lpr × C3H/lpr)F2 intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium-sized arteries in the lower limbs. Genomic DNA samples from F2 intercross mice were examined by simple sequence-length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci. Results. A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of mediumsized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys. Conclusion. Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.

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Genetic basis of tissue specificity of vasculitis in MRL/lpr mice

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