title: Arrested natural killer cell development associated with transgene insertion into the Atf2 locus.
abstract: Natural killer (NK) cell development in the bone marrow is not fully understood. Following lineage commitment, these cells appear to advance through a series of developmental stages that are beginning to be characterized. We previously reported a selective deficiency of NK cells in a C57BL/6 mouse with a transgenic construct consisting of the cDNA for the Ly49A major histocompatibility complex (MHC) class 1-specific inhibitory receptor driven by the granzyme A gene. This mouse has few NK cells in peripheral tissues with relative preservation of other immune cells, including T and B cells. Herein we demonstrate that these mice have an accumulation of NK cells with an immature phenotype in the bone marrow, consistent with a block at a previously proposed stage in normal NK-cell development. The phenotype is associated with transgenic insertion into Atf2, the gene for the basic leucine zipper (bZIP) transcription factor family member ATF-2. Although analysis of Atf2-null NK cells shows no defect, the transgenic mice express abnormal truncated Atf2 transcripts that may mediate a repressor effect because ATF2 can heterodimerize with other bZIP molecules. The defect is cell intrinsic, suggesting that certain bZIP molecules play significant roles in NK-cell development.
authors.affiliation: Howard Hughes Medical Institute, the Rheumatology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Song
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Higuchi
authors.forename: Hyunseok P
authors.initials: HP
authors.lastname: Kang
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Pratt
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.forename: Caron M
authors.initials: CM
authors.lastname: Hong
authors.forename: Jennifer
authors.initials: J
authors.lastname: Poursine-Laurent
authors.forename: Koho
authors.initials: K
authors.lastname: Iizuka
authors.forename: Anthony R
authors.initials: AR
authors.lastname: French
authors.forename: John B
authors.initials: JB
authors.lastname: Sunwoo
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Reimold
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional / Q000235:genetics / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A; D040641:Quantitative Trait Loci / Q000235:genetics / Q000276:immunology*; D055630:Receptors, NK Cell Lectin-Like; D019076:Transgenes / Q000235:genetics / Q000276:immunology*; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology
chemical_list: D051698:Activating Transcription Factor 2; D000950:Antigens, Ly; C497106:Atf2 protein, mouse; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like