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

Oral Medicine and Surgery

Research output: Contribution to journal › Article

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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Yamada, A., Miyazaki, T., Lu, L. M., Ono, M., Ito, M. R., Terada, M., Mori, S., Hata, K., Nozaki, Y., Nakatsuru, S., Nakamura, Y., Onji, M., & Nose, M. (2003). Genetic basis of tissue specificity of vasculitis in MRL/lpr mice. Arthritis and Rheumatism, 48(5), 1445-1451. https://doi.org/10.1002/art.10952

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.

Research output: Contribution to journal › Article

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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",

year = "2003",

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doi = "10.1002/art.10952",

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T1 - Genetic basis of tissue specificity of vasculitis in MRL/lpr mice

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

Y1 - 2003/5/1

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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