title: Defect in rearrangement of the most 5' TCR-J alpha following targeted deletion of T early alpha (TEA): implications for TCR alpha locus accessibility.
abstract: To address the role of the TEA germline transcription, which initiates upstream of the TCR-J alpha S, in the regulation of TCR-J alpha locus accessibility, we created a mouse in which this region has been removed by homologous recombination. Normal development of T alpha beta cells and the expression of other TCR alpha germline transcripts in TEA-/- mice ruled out an exclusive role for TEA in the overall accessibility of the J alpha cluster. However, the rearrangement of the most 5' J alpha (J alpha 61 to J alpha 53) was severely impaired, indicating that TEA may control the DNA accessibility of a particular J alpha window. Moreover, the relative usage of every J alpha segment was affected. These results are consistent with TEA acting as a "rearrangement-focusing" element, targeting the primary waves of V alpha-J alpha recombination to the most 5' J alpha S in an ongoing TCR-J alpha rearrangement model.
authors.affiliation: Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Villey
authors.forename: D
authors.initials: D
authors.lastname: Caillol
authors.forename: F
authors.initials: F
authors.lastname: Selz
authors.forename: P
authors.initials: P
authors.lastname: Ferrier
authors.forename: J P
authors.initials: JP
authors.lastname: de Villartay
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA