Congenic Mice Provide Evidence for a Genetic Locus That Modulates Spontaneous Arthritis Caused by Deficiency of IL-1RA

Yanhong Cao, Xiaoyun Liu, Nan Deng, Yan Jiao, Yonghui Ma, Karen Hasty, John Stuart, Weikuan Gu

Research output: Contribution to journalArticle

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Abstract

To understand the role of genetic factors involved in the development of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we have identified a genomic region containing a major quantitative trait locus (QTL) for this disease. The QTL is on chromosome 1 and appears to be the strongest genetic region regulating arthritis. To confirm the importance of the QTL and to identify potential candidate genes within it, we conducted speed congenic breeding to transfer the QTL region from DBA/1 mice that are resistant to spontaneous arthritis into BALB/c-/- which are susceptible. Genetic markers along every chromosome were used to assist in the selection of progeny in each generation to backcross to BALB/c-/-. By the 6th generation we determined that all of the chromosomes in the progeny were of BALB/c origin with the exception of portions of chromosome 1. At this stage we intercrossed selected mice to produce homozygous strains containing the genomic background of BALB/c-/- except for the QTL region on chromosome 1, which was from DBA/1. We were able to establish two congenic strains with overlapping DBA/1 DNA segments. These strains were observed for the development of spontaneous arthritis. Both congenic strains were relatively resistant to spontaneous arthritis and had delayed onset and reduced severity of disease. The gene/s that regulates this major QTL would appear to be located in the region of the QTL that is shared by both strains. The common transferred region is between D1Mit110 and D1Mit209 on chromosome 1. We evaluated this region for candidate genes and have identified a limited number of candidates. Confirmation of the identity and precise role of the candidates will require additional study.

Original languageEnglish (US)
Article numbere68158
JournalPLoS ONE
Volume8
Issue number6
DOIs
StatePublished - Jun 28 2013

Fingerprint

Congenic Mice
Genetic Loci
Quantitative Trait Loci
arthritis
Chromosomes
Arthritis
quantitative trait loci
Chromosomes, Human, Pair 1
loci
chromosomes
mice
Genes
Interleukin-1 Receptors
genomics
Inbred DBA Mouse
genes
interleukin-1
Genetic Markers
disease severity
Breeding

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Congenic Mice Provide Evidence for a Genetic Locus That Modulates Spontaneous Arthritis Caused by Deficiency of IL-1RA. / Cao, Yanhong; Liu, Xiaoyun; Deng, Nan; Jiao, Yan; Ma, Yonghui; Hasty, Karen; Stuart, John; Gu, Weikuan.

In: PLoS ONE, Vol. 8, No. 6, e68158, 28.06.2013.

Research output: Contribution to journalArticle

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