Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genesReportar como inadecuado




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Arthritis Research and Therapy

, 11:R10

First Online: 20 January 2009Received: 18 July 2008Revised: 02 December 2008Accepted: 20 January 2009

Abstract

IntroductionIn a cross between two mouse strains, the susceptible B10.RIII H-2 and resistant RIIIS-J H-2 strains, a locus on mouse chromosome 5 Eae39 was previously shown to control experimental autoimmune encephalomyelitis EAE. Recently, quantitative trait loci QTL, linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis CIA.

MethodsCIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by micro-satellite mapping and statistics was calculated by standard methods.

ResultsExperiments of CIA in Eae39 congenic- and sub-interval congenic mice, carrying RIIIS-J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair Mbp interval that regulates disease.

ConclusionsDisease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases.

AbbreviationsAUCarea under curve

BSAbovine serum albumin

CIAcollagen-induced arthritis

CNScentral nervous system

EAEexperimental autoimmune encephalomyelitis

ELISAenzyme-linked immunosorbent assay

FPfront primer

IFAincomplete Freund-s adjuvant

Igimmunoglobulin

Mbpmega base pairs

MHCmajor histocompatibility complex

MSmultiple sclerosis

PBSphosphate-buffered saline

PCRpolymerase chain reaction

QTLquantitative trait locus

RArheumatoid arthritis

RPreverse primer.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2597 contains supplementary material, which is available to authorized users.

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Autor: Therese Lindvall - Jenny Karlsson - Rikard Holmdahl - Åsa Andersson

Fuente: https://link.springer.com/







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