Backcross and partial advanced intercross analysis of nonobese diabetic gene-mediated effects on collagen-induced arthritis reveals an interactive effect by two major loci.
Lindqvist, Anna-Karin LU ; Johannesson, Martina LU ; Johansson, Åsa LU ; Nandakumar, Kutty S ; Blom, Anna LU
and Holmdahl, Rikard
LU
(2006)
In Journal of Immunology
177(6).
p.3952-3959
- Abstract
- Genetic segregation analysis between NOD and C57BL strains have been used to identify loci associated with autoimmune disease. Only two loci (Cia2 and Cia9) had earlier been found to control development of arthritis, whereas none of the previously identified diabetes loci was of significance for arthritis. We have now made a high-powered analysis of a backcross of NOD genes on to the B10.Q strain for association with collagen-induced arthritis. We could confirm relevance of both Cia2 and Cia9 as well as the interaction between them, but we did not identify any other significant arthritis loci. Immune cellular subtyping revealed that Cia2 was also associated with the number of blood macrophages. Congenic strains of the Cia2 and Cia9 loci on... (More)
- Genetic segregation analysis between NOD and C57BL strains have been used to identify loci associated with autoimmune disease. Only two loci (Cia2 and Cia9) had earlier been found to control development of arthritis, whereas none of the previously identified diabetes loci was of significance for arthritis. We have now made a high-powered analysis of a backcross of NOD genes on to the B10.Q strain for association with collagen-induced arthritis. We could confirm relevance of both Cia2 and Cia9 as well as the interaction between them, but we did not identify any other significant arthritis loci. Immune cellular subtyping revealed that Cia2 was also associated with the number of blood macrophages. Congenic strains of the Cia2 and Cia9 loci on the B10.Q background were made and used to establish a partial advanced intercross (PAI). Testing the PAI mice for development of collagen-induced arthritis confirmed the loci and the interactions and also indicated that at least two genes contribute to the Cia9 locus. Furthermore, it clearly showed that Cia2 is dominant protective but that the protection is not complete. Because these results may indicate that the Cia2 effect on arthritis is not only due to the deficiency of the complement C5, we analyzed complement functions in the Cia2 congenics as well as the PAI mice. These data show that not only arthritis but also C5-dependent complement activity is dominantly suppressed, confirming that C5 is one of the major genes explaining the Cia2 effect. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/161241
- author
- Lindqvist, Anna-Karin
LU
; Johannesson, Martina
LU
; Johansson, Åsa
LU
; Nandakumar, Kutty S
; Blom, Anna
LU
and Holmdahl, Rikard
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 177
- issue
- 6
- pages
- 3952 - 3959
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000240475300051
- pmid:16951358
- scopus:33748567828
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical Chemistry, Malmö (013016000), Medical Inflammation Research (013212019), Department of Translational Medicine (013017500)
- id
- 67f50828-3082-4447-8b95-9d90506d28be (old id 161241)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16951358&dopt=Abstract
- date added to LUP
- 2016-04-01 15:18:16
- date last changed
- 2022-03-22 03:47:30
@article{67f50828-3082-4447-8b95-9d90506d28be,
abstract = {{Genetic segregation analysis between NOD and C57BL strains have been used to identify loci associated with autoimmune disease. Only two loci (Cia2 and Cia9) had earlier been found to control development of arthritis, whereas none of the previously identified diabetes loci was of significance for arthritis. We have now made a high-powered analysis of a backcross of NOD genes on to the B10.Q strain for association with collagen-induced arthritis. We could confirm relevance of both Cia2 and Cia9 as well as the interaction between them, but we did not identify any other significant arthritis loci. Immune cellular subtyping revealed that Cia2 was also associated with the number of blood macrophages. Congenic strains of the Cia2 and Cia9 loci on the B10.Q background were made and used to establish a partial advanced intercross (PAI). Testing the PAI mice for development of collagen-induced arthritis confirmed the loci and the interactions and also indicated that at least two genes contribute to the Cia9 locus. Furthermore, it clearly showed that Cia2 is dominant protective but that the protection is not complete. Because these results may indicate that the Cia2 effect on arthritis is not only due to the deficiency of the complement C5, we analyzed complement functions in the Cia2 congenics as well as the PAI mice. These data show that not only arthritis but also C5-dependent complement activity is dominantly suppressed, confirming that C5 is one of the major genes explaining the Cia2 effect.}},
author = {{Lindqvist, Anna-Karin and Johannesson, Martina and Johansson, Åsa and Nandakumar, Kutty S and Blom, Anna and Holmdahl, Rikard}},
issn = {{1550-6606}},
language = {{eng}},
number = {{6}},
pages = {{3952--3959}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Backcross and partial advanced intercross analysis of nonobese diabetic gene-mediated effects on collagen-induced arthritis reveals an interactive effect by two major loci.}},
url = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16951358&dopt=Abstract}},
volume = {{177}},
year = {{2006}},
}