Arrested natural killer cell development associated with transgene insertion into the Atf2 locus.
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.
Kim
Sungjin
S
Howard Hughes Medical Institute, the Rheumatology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Song
Yun-Jeong
YJ
Higuchi
Darryl A
DA
Kang
Hyunseok P
HP
Pratt
Jennifer R
JR
Yang
Liping
L
Hong
Caron M
CM
Poursine-Laurent
Jennifer
J
Iizuka
Koho
K
French
Anthony R
AR
Sunwoo
John B
JB
Ishii
Shunsuke
S
Reimold
Andreas M
AM
Yokoyama
Wayne M
WM
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
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