PMID- 14978078
OWN - NLM
STAT- MEDLINE
DCOM- 20040621
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 172
IP  - 5
DP  - 2004 Mar 1
TI  - The centromeric region of chromosome 7 from MRL mice (Lmb3) is an epistatic 
      modifier of Fas for autoimmune disease expression.
PG  - 2785-94
AB  - Lupus is a prototypic systemic autoimmune disease that has a significant genetic 
      component in its etiology. Several genome-wide screens have identified multiple 
      loci that contribute to disease susceptibility in lupus-prone mice, including the 
      Fas-deficient MRL/Fas(lpr) strain, with each locus contributing in a threshold 
      liability manner. The centromeric region of chromosome 7 was identified as a 
      lupus susceptibility locus in MRL/Fas(lpr) mice as Lmb3. This locus was 
      backcrossed onto the resistant C57BL/6 (B6) background, in the presence or 
      absence of Fas, resulting in the generation of B6.MRLc7 congenic animals. 
      Detailed analysis of these animals showed that Lmb3 enhances and accelerates 
      several characteristics of lupus, including autoantibody production, kidney 
      disease, and T cell activation, as well as accumulation of CD4(-)CD8(-) 
      double-negative T cells, the latter a feature of Fas-deficient mice. These 
      effects appeared to be dependent on the interaction between Lmb3 and Fas 
      deficiency, as Lmb3 on the B6/+(Fas-lpr) background did not augment any of the 
      lupus traits measured. These findings confirm the role of Lmb3 in lupus 
      susceptibility, as a modifier of Fas(lpr) phenotype, and illustrate the 
      importance of epistatic interaction between genetic loci in the etiology of 
      lupus. Furthermore, they suggest that the genetic lesion(s) in MRLc7 is probably 
      different from those in NZMc7 (Sle3/5), despite a significant overlap of these 
      two intervals.
FAU - Kong, Philip L
AU  - Kong PL
AD  - Section of Rheumatology, Department of Internal Medicine, and Section of 
      Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
FAU - Morel, Laurence
AU  - Morel L
FAU - Croker, Byron P
AU  - Croker BP
FAU - Craft, Joseph
AU  - Craft J
LA  - eng
GR  - AR40072/AR/NIAMS NIH HHS/United States
GR  - AR44076/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Autoantibodies)
RN  - 0 (Genetic Markers)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Animals
MH  - Autoantibodies/biosynthesis
MH  - Centromere/*immunology
MH  - *Epistasis, Genetic
MH  - Female
MH  - Genetic Markers/*immunology
MH  - *Genetic Predisposition to Disease
MH  - Immunophenotyping
MH  - Lupus Erythematosus, Systemic/*genetics/*immunology/pathology
MH  - Lupus Nephritis/genetics/immunology/pathology
MH  - Lymphocyte Subsets/pathology
MH  - Male
MH  - Mice
MH  - Mice, Congenic
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred MRL lpr
MH  - Phenotype
MH  - fas Receptor/*genetics
EDAT- 2004/02/24 05:00
MHDA- 2004/06/23 05:00
CRDT- 2004/02/24 05:00
PHST- 2004/02/24 05:00 [pubmed]
PHST- 2004/06/23 05:00 [medline]
PHST- 2004/02/24 05:00 [entrez]
AID - 10.4049/jimmunol.172.5.2785 [doi]
PST - ppublish
SO  - J Immunol. 2004 Mar 1;172(5):2785-94. doi: 10.4049/jimmunol.172.5.2785.