Arrested natural killer cell development associated with transgene insertion into the Atf2 locus

Sung Jin Kim, Yun Jeong Song, Darryl A. Higuchi, Hyunseok P. Kang, Jennifer R. Pratt, Liping Yang, Caron M. Hong, Jennifer Poursine-Laurent, Koho Iizuka, Anthony R. French, John B. Sunwoo, Shunsuke Ishii, Andreas M. Reimold, Wayne M. Yokoyama

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 NKcell development.

Original languageEnglish (US)
Pages (from-to)1024-1030
Number of pages7
JournalBlood
Volume107
Issue number3
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Fingerprint

Leucine Zippers
Transgenes
Natural Killer Cells
Bone
Genes
Basic-Leucine Zipper Transcription Factors
Granzymes
Defects
Molecules
Complementary DNA
Cells
Tissue
Bone Marrow
Phenotype
Null Lymphocytes
Major Histocompatibility Complex
Inbred C57BL Mouse
Transgenic Mice
B-Lymphocytes
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Kim, S. J., Song, Y. J., Higuchi, D. A., Kang, H. P., Pratt, J. R., Yang, L., ... Yokoyama, W. M. (2006). Arrested natural killer cell development associated with transgene insertion into the Atf2 locus. Blood, 107(3), 1024-1030. https://doi.org/10.1182/blood-2005-04-1493

Arrested natural killer cell development associated with transgene insertion into the Atf2 locus. / Kim, Sung Jin; Song, Yun Jeong; Higuchi, Darryl A.; Kang, Hyunseok P.; Pratt, Jennifer R.; Yang, Liping; Hong, Caron M.; Poursine-Laurent, Jennifer; Iizuka, Koho; French, Anthony R.; Sunwoo, John B.; Ishii, Shunsuke; Reimold, Andreas M.; Yokoyama, Wayne M.

In: Blood, Vol. 107, No. 3, 01.02.2006, p. 1024-1030.

Research output: Contribution to journalArticle

Kim, SJ, Song, YJ, Higuchi, DA, Kang, HP, Pratt, JR, Yang, L, Hong, CM, Poursine-Laurent, J, Iizuka, K, French, AR, Sunwoo, JB, Ishii, S, Reimold, AM & Yokoyama, WM 2006, 'Arrested natural killer cell development associated with transgene insertion into the Atf2 locus', Blood, vol. 107, no. 3, pp. 1024-1030. https://doi.org/10.1182/blood-2005-04-1493
Kim, Sung Jin ; Song, Yun Jeong ; Higuchi, Darryl A. ; Kang, Hyunseok P. ; Pratt, Jennifer R. ; Yang, Liping ; Hong, Caron M. ; Poursine-Laurent, Jennifer ; Iizuka, Koho ; French, Anthony R. ; Sunwoo, John B. ; Ishii, Shunsuke ; Reimold, Andreas M. ; Yokoyama, Wayne M. / Arrested natural killer cell development associated with transgene insertion into the Atf2 locus. In: Blood. 2006 ; Vol. 107, No. 3. pp. 1024-1030.
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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 NKcell development.",
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