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Titolo:
Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22(a) lupus-prone mice
Autore:
Mary, C; Laporte, C; Parzy, D; Santiago, ML; Stefani, F; Lajaunias, F; Parkhouse, RME; OKeefe, TL; Neuberger, MS; Izui, S; Reininger, L;
Indirizzi:
Fac Med Marseille, INSERM, Unite 399, F-13385 Marseille 05, France Fac MedMarseille Marseille France 05 399, F-13385 Marseille 05, France Serv Sante Armees, Inst Trop Med, Marseille, France Serv Sante Armees Marseille France es, Inst Trop Med, Marseille, France Univ Geneva, Dept Pathol, CH-1211 Geneva, Switzerland Univ Geneva GenevaSwitzerland CH-1211 thol, CH-1211 Geneva, Switzerland Inst Anim Hlth, Pirbright, England Inst Anim Hlth Pirbright EnglandInst Anim Hlth, Pirbright, England MRC, Mol Biol Lab, Cambridge CB2 2QH, England MRC Cambridge England CB2 2QH , Mol Biol Lab, Cambridge CB2 2QH, England
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 6, volume: 165, anno: 2000,
pagine: 2987 - 2996
SICI:
0022-1767(20000915)165:6<2987:DEOTCG>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE-PHOSPHATASE 1C; LYN-DEFICIENT MICE; CONGENIC MOUSE STRAINS; B-CELLS; AUTOANTIBODY PRODUCTION; CD22-DEFICIENT MICE; AUTOIMMUNE-DISEASE; NEGATIVE REGULATOR; ADHESION MOLECULE; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Reininger, L Fac Med Marseille, INSERM, Unite 399, 27 Blvd Jean Moulin, F-13385 Marseille 05, France Fac Med Marseille 27 Blvd Jean Moulin MarseilleFrance 05 ce
Citazione:
C. Mary et al., "Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22(a) lupus-prone mice", J IMMUNOL, 165(6), 2000, pp. 2987-2996

Abstract

The Cd22 gene encodes a B cell-specific adhesion molecule that modulates Bcell Ag receptor-mediated signal transduction, and is allelic to a lupus-susceptibility locus in New Zealand White (NZW) mice. In this study, we showthat, in addition to the wild-type transcripts, NZW (Cd22(a)) mice synthesize aberrant CD22 mRNAs that contain similar to 20-120 nucleotide insertions upstream of the coding region between exons 2 and 3, and/or similar to 100-190 nucleotide deletions of exon 4, Sequence analysis revealed that theseaberrant mRNA species arose by alternative splicing due to the presence inthe NZW strain of a 794-bp sequence insertion in the second intron, containing a fluster of short interspersed nucleotide elements. Both the presenceof sequence insertion and aberrantly spliced mRNAs were specific to mice bearing the Cd22(a) and Cd22(c) alleles, Up-regulation of CD22 expression after LPS activation appeared impaired in Cd22(a) spleen cells (twice lower than in Cd22(b) B cells). Furthermore, we show that partial CD22 deficiency,i.e., heterozygous level of CD22 expression, markedly promotes the production of IgG anti-DNA autoantibodies in C57BL/6 (Cd22(b)) mice bearing the Y chromosome-linked autoimmune acceleration gene, Yaa, Taken together, these results suggest that a lower up-regulation of CD22 on activated B cells (resulting from Cd22 gene anomaly in Cd22(a) mice or from CD22 heterozygosity in mutants obtained by gene targeting) is implicated in autoantibody production, providing support for Cd22(a) as a possible candidate allele contributing to lupus susceptibility.

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Documento generato il 02/04/20 alle ore 19:25:54