Quest for arthritis-causative genetic factors in the rat.

Abstract:

:Experimental rat models of arthritis are extensively studied with a view to understand the genetic underpinnings of rheumatoid arthritis (RA). Genome scans using these models have led to the detection of arthritis regulatory quantitative trait loci (QTLs) on all but three chromosomes of the rat. Whereas some of the QTLs are model specific, others overlap between models. Some arthritis susceptibility and/or severity QTLs identified by genetic linkage analyses are corroborated by substitution mapping using congenic strains, whereas others are not. In these cases, testing alternate arthritis models proved to be useful to identify QTL effects. Nevertheless, development and testing of congenic substrains containing progressively shorter introgressed regions have not only fine mapped the location of the arthritis QTLs but also resulted in the identification of multiple QTLs within several originally identified individual QTL. Most of these studies progressed rapidly since 2001, when the rat genome sequence was published. Proof of principle for substitution mapping as a successful method for QTL gene discovery is provided by the positional cloning of Ncf1 as one of the arthritis QTLs in rats. This finding is encouraging for similar sustained dissection of all the other arthritis QTLs mapped in the rat. Identification of rat arthritis QTLs is expected to pave the way for discovery of yet-unidentified arthritis-causative genetic elements and/or pathways for RA in humans and potential development of targeted therapeutics. This review catalogs some of the recent advances made in QTL discovery projects of experimentally induced rat models of arthritis.

journal_name

Physiol Genomics

journal_title

Physiological genomics

authors

Joe B

doi

10.1152/physiolgenomics.00034.2005

subject

Has Abstract

pub_date

2006-10-03 00:00:00

pages

1-11

issue

1

eissn

1094-8341

issn

1531-2267

pii

00034.2005

journal_volume

27

pub_type

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