PMID- 19238339
OWN - NLM
STAT- MEDLINE
DCOM- 20090706
LR  - 20211020
IS  - 1432-1777 (Electronic)
IS  - 0938-8990 (Linking)
VI  - 20
IP  - 3
DP  - 2009 Mar
TI  - Genome-wide search for genes that modulate inflammatory arthritis caused by Ali18 
      mutation in mice.
PG  - 152-61
LID - 10.1007/s00335-009-9170-0 [doi]
AB  - Many of inflammatory diseases, including inflammatory arthritis, are 
      multifactorial bases. The Ali18 semidominant mutation induced by 
      N-ethyl-N-nitrosourea in the C3HeB/FeJ (C3H) genome causes spontaneous 
      inflammation of peripheral limbs and elevated immunoglobulin E (IgE) levels in 
      mice. Although the Ali18 locus was mapped to a single locus on chromosome 4, the 
      arthritic phenotype of Ali18/+ mice was completely suppressed in F1 hybrid 
      genetic backgrounds. To determine the chromosomal locations of the modifier loci 
      affecting the severity of arthritis, an autosomal genome scan of 22 affected 
      Ali18/+ F2 mice was conducted using C57BL/6J as a partner strain. Interestingly, 
      regions on chromosomes 1 and 3 in C3H showed significant genetic interactions. 
      Moreover, 174 N2 (backcross to Ali18/Ali18) and 267 F2 animals were used for 
      measurement of arthritis scores and plasma IgE levels, and also for genotyping 
      with 153 genome-wide single nucleotide polymorphism (SNP) markers. In N2 
      populations, two significant trait loci for arthritis scores on chromosomes 1 and 
      15 were detected. Although no significant scores were detected in F2 mice besides 
      chromosome 4, a suggestive score was detected on chromosome 3. In addition, a 
      two-dimensional genome scan using F2 identified five suggestive scores of 
      chromosomal combinations, chromosomes 1 x 10, 2 x 6, 3 x 4, 4 x 9, and 6 x 15. No 
      significant trait loci affecting IgE levels were detected in both N2 and F2 
      populations. Identification of the Ali18 modifier genes by further detailed 
      analyses such as congenic strains and expression profiling may dissect molecular 
      complexity in inflammatory diseases.
FAU - Abe, Koichiro
AU  - Abe K
AD  - Division of Basic Medical Science and Molecular Medicine, Tokai University School 
      of Medicine, Shimokasuya 143, Isehara, Kanagawa, 259-1193, Japan. 
      abeko@is.icc.u-tokai.ac.jp
FAU - Klaften, Matthias
AU  - Klaften M
FAU - Narita, Akira
AU  - Narita A
FAU - Kimura, Tetsuaki
AU  - Kimura T
FAU - Imai, Kenji
AU  - Imai K
FAU - Kimura, Minoru
AU  - Kimura M
FAU - Rubio-Aliaga, Isabel
AU  - Rubio-Aliaga I
FAU - Wagner, Sibylle
AU  - Wagner S
FAU - Jakob, Thilo
AU  - Jakob T
FAU - Hrabe de Angelis, Martin
AU  - Hrabe de Angelis M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090224
PL  - United States
TA  - Mamm Genome
JT  - Mammalian genome : official journal of the International Mammalian Genome Society
JID - 9100916
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Animals
MH  - Arthritis/*genetics/immunology
MH  - Arthritis, Experimental/genetics/immunology
MH  - Chromosome Mapping
MH  - Chromosomes, Mammalian/genetics
MH  - Crosses, Genetic
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - *Mutation
MH  - Polymorphism, Single Nucleotide
EDAT- 2009/02/25 09:00
MHDA- 2009/07/07 09:00
CRDT- 2009/02/25 09:00
PHST- 2008/08/23 00:00 [received]
PHST- 2008/12/30 00:00 [accepted]
PHST- 2009/02/25 09:00 [entrez]
PHST- 2009/02/25 09:00 [pubmed]
PHST- 2009/07/07 09:00 [medline]
AID - 10.1007/s00335-009-9170-0 [doi]
PST - ppublish
SO  - Mamm Genome. 2009 Mar;20(3):152-61. doi: 10.1007/s00335-009-9170-0. Epub 2009 Feb 
      24.