A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains.

A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Research Abstract Details 

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A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Abstract Text:

An intercross between atherosclerosis susceptible (C57BL/6J ApoE0) and resistant (FVB/N ApoE0) mice revealed a susceptibility locus on chromosome 10 (11 cM, logarithm of odds 7.8). Surprisingly, the genotypic means for this locus revealed that heterozygosity or homozygosity for the C57BL/6J allele was associated with decreased atherosclerosis. A candidate gene in this region is A20, which is involved in the feedback suppression of NFkappaB activation induced by tumor necrosis factor alpha (TNFalpha). We sequenced the A20 gene coding region from the parental strains and found a single-nucleotide polymorphism resulting in a single amino acid exchange, Glu627Ala (C57BL/6J vs. FVB/N). This mutation introduces a putative casein kinase 2 phosphorylation site in C57BL/6J-A20 not present in FVB/N-A20. NFkappaB reporter gene assays showed that this amino acid change results in less effective termination of TNFalpha-stimulated NFkappaB activation by C57BL/6J-A20. In accordance, the TNFalpha-induced expression of NFkappaB target genes (A20, IkappaBalpha) in vascular smooth muscle cells was prolonged in cells isolated from C57BL/6J compared with FVB/N mice. In light of the genotypic means for atherosclerosis at the chromosome 10 locus in F2 mice from this intercross, the observations now reported suggest that prolonged expression of genes induced by NFkappaB might be antirather than proatherogenic.

A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Publishing Authors By Initials

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 100

Page Numbers: 14235-40

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 12

MONTH: 11

YEAR: 2003

A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: pharmacology

Chemical & Substance for Abstract: A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains. Information

Substance Name: Tnfaip3 protein, mouse

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for A20, a regulator of NFkappaB, maps to an atherosclerosis locus and differs between parental sensitive C57BL/6J and resistant FVB/N strains.

AFFILIATION: Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, Box 179, 1230 York Avenue, New York, NY 10021, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL54591-08

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

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