Cargando…
Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA
BACKGROUND: To understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1(−/−) mice that are resistant to spontaneou...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272550/ https://www.ncbi.nlm.nih.gov/pubmed/25488730 http://dx.doi.org/10.1186/s12865-014-0057-9 |
_version_ | 1782349734318440448 |
---|---|
author | Deng, Nan Jiao, Yan Cao, Yanhong Liu, Xiaoyun Ma, Yonghui Hasty, Karen A Brand, David D Stuart, John M Gu, Weikuan |
author_facet | Deng, Nan Jiao, Yan Cao, Yanhong Liu, Xiaoyun Ma, Yonghui Hasty, Karen A Brand, David D Stuart, John M Gu, Weikuan |
author_sort | Deng, Nan |
collection | PubMed |
description | BACKGROUND: To understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1(−/−) mice that are resistant to spontaneous arthritis into BALB/c(−/−) mice which are susceptible. We were able to establish two congenic strains which exhibited a delayed onset and reduced severity of disease. In this study, we asked a different set of questions. How will the QTL region from BALB/c(−/−) interact with the rest of the genome in the DBA/1(−/−) background? Will the DBA/1(−/−) mice become susceptible to spontaneous arthritis if the QTL genomic region on chromosome 1 was replaced with the genomic fragment of the same region from BALB/c(−/−)? We conducted the congenic breeding with the similar procedure as that of congenic strains with BALB/c(−/−) background. RESULT: Instead of BALB/c(−/−), DBA/1(−/−) was used as the recurrent parent while BALB/c(−/−) was used as the donor parent. By the 6(th) generation we determined that all of the chromosomes in the progeny were of DBA/1(−/−) origin with the exception of the QTL portion of chromosome 1 which is heterozygous of BALB/c(−/−) and DBA/1(−/−) origin. We then intercrossed selected mice to produce homozygous strains containing the homozygous genomic region of BALB/c(−/−) on chromosome 1, while the rest of genome are homozygous DBA/1(−/−). This strain was observed for the development of spontaneous arthritis. Up to 9 weeks of age, both congenic strain and DBA/1(−/−) did not develop arthritis. However, after 9 weeks, the congenic strain started to exhibit signs of arthritis, while the DBA/1(−/−) remained free from disease. CONCLUSION: The result indicates a strong influence of genetic factor(s) on the QTL of chromosome 1 on the susceptibility to spontaneous arthritis. Identification of genetic factors within this QTL region in the future will significantly enhance our understanding of molecular mechanism of spontaneous arthritis. |
format | Online Article Text |
id | pubmed-4272550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42725502014-12-21 Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA Deng, Nan Jiao, Yan Cao, Yanhong Liu, Xiaoyun Ma, Yonghui Hasty, Karen A Brand, David D Stuart, John M Gu, Weikuan BMC Immunol Research Article BACKGROUND: To understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1(−/−) mice that are resistant to spontaneous arthritis into BALB/c(−/−) mice which are susceptible. We were able to establish two congenic strains which exhibited a delayed onset and reduced severity of disease. In this study, we asked a different set of questions. How will the QTL region from BALB/c(−/−) interact with the rest of the genome in the DBA/1(−/−) background? Will the DBA/1(−/−) mice become susceptible to spontaneous arthritis if the QTL genomic region on chromosome 1 was replaced with the genomic fragment of the same region from BALB/c(−/−)? We conducted the congenic breeding with the similar procedure as that of congenic strains with BALB/c(−/−) background. RESULT: Instead of BALB/c(−/−), DBA/1(−/−) was used as the recurrent parent while BALB/c(−/−) was used as the donor parent. By the 6(th) generation we determined that all of the chromosomes in the progeny were of DBA/1(−/−) origin with the exception of the QTL portion of chromosome 1 which is heterozygous of BALB/c(−/−) and DBA/1(−/−) origin. We then intercrossed selected mice to produce homozygous strains containing the homozygous genomic region of BALB/c(−/−) on chromosome 1, while the rest of genome are homozygous DBA/1(−/−). This strain was observed for the development of spontaneous arthritis. Up to 9 weeks of age, both congenic strain and DBA/1(−/−) did not develop arthritis. However, after 9 weeks, the congenic strain started to exhibit signs of arthritis, while the DBA/1(−/−) remained free from disease. CONCLUSION: The result indicates a strong influence of genetic factor(s) on the QTL of chromosome 1 on the susceptibility to spontaneous arthritis. Identification of genetic factors within this QTL region in the future will significantly enhance our understanding of molecular mechanism of spontaneous arthritis. BioMed Central 2014-12-09 /pmc/articles/PMC4272550/ /pubmed/25488730 http://dx.doi.org/10.1186/s12865-014-0057-9 Text en © Deng et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Deng, Nan Jiao, Yan Cao, Yanhong Liu, Xiaoyun Ma, Yonghui Hasty, Karen A Brand, David D Stuart, John M Gu, Weikuan Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA |
title | Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA |
title_full | Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA |
title_fullStr | Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA |
title_full_unstemmed | Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA |
title_short | Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA |
title_sort | genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of il-1ra |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272550/ https://www.ncbi.nlm.nih.gov/pubmed/25488730 http://dx.doi.org/10.1186/s12865-014-0057-9 |
work_keys_str_mv | AT dengnan genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT jiaoyan genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT caoyanhong genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT liuxiaoyun genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT mayonghui genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT hastykarena genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT branddavidd genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT stuartjohnm genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra AT guweikuan genomiclocusonchromosome1regulatessusceptibilitytospontaneousarthritisinmicedeficiencyofil1ra |