Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA.
BMC Immunol
; 15: 57, 2014 Dec 09.
Article
en En
| MEDLINE
| ID: mdl-25488730
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Artritis
/
Cromosomas de los Mamíferos
/
Sitios de Carácter Cuantitativo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
BMC Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos