Arrested natural killer cell development associated with transgene insertion into the Atf2 locus.
Blood
; 107(3): 1024-30, 2006 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-16223777
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Diferenciación Celular
/
Mutagénesis Insercional
/
Transgenes
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Sitios de Carácter Cuantitativo
/
Factor de Transcripción Activador 2
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos