title: Complete sequence determination of the mouse and human CTLA4 gene loci: cross-species DNA sequence similarity beyond exon borders.
abstract: CTLA4 (CD152), a receptor for the B7 costimulatory molecules (CD80 and CD86), is considered a fundamental regulator of T-cell activation. In this paper, we present the complete primary structure of the mouse and human CTLA4 gene loci. Sequence comparison between the mouse and the human CTLA4 gene loci revealed a high degree of sequence conservation both for homologous noncoding regions (65-78% identity) and for coding regions (72-98% identity), with an overall score of 71% over the entire length of the two genes. Of the CTLA4 genomic regions aligned, five simple repetitive elements were found in the mouse locus, whereas two simple repetitive sequences were localized on the human locus. RNA blot analysis of mouse and human primary tissues indicated that both CTLA4 and T-cell receptor transcripts were found in most organs with generally higher levels in lymphoid tissues. The conservation of CTLA4 gene patterning raises the possibility that constrained gene evolution of CTLA4 may be linked to conserved transcriptional control of this locus.
authors.affiliation: Department of Immunology, Genetics Institute, 87 CambridgePark Drive, Cambridge, Massachusetts 02140, USA. Vling@genetics.com
authors.forename: V
authors.initials: V
authors.lastname: Ling
authors.forename: P W
authors.initials: PW
authors.lastname: Wu
authors.forename: H F
authors.initials: HF
authors.lastname: Finnerty
authors.forename: A H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: G S
authors.initials: GS
authors.lastname: Gray
authors.forename: M
authors.initials: M
authors.lastname: Collins
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D060908:CTLA-4 Antigen; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003429:Cross Reactions / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D012313:RNA / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D017421:Sequence Analysis; D020539:Sequence Analysis, Protein; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014018:Tissue Distribution / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D012313:RNA; D000069594:Abatacept; D004247:DNA