A novel conditional NPM-ALK-driven model of CD30+ T-cell lymphoma mediated by a translational stop cassette.
Animals
Apoptosis
Cell Proliferation
Female
Humans
Ki-1 Antigen
/ metabolism
Lymphoma, Large-Cell, Anaplastic
/ genetics
Lymphoma, T-Cell
/ genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Protein Processing, Post-Translational
Protein-Tyrosine Kinases
/ genetics
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
07
09
2018
accepted:
12
06
2019
revised:
02
05
2019
pubmed:
23
11
2019
medline:
25
11
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
Targeted expression of transgenes is essential for the accurate representation of human disease in in vivo models. Current approaches to generate conditional transgenic mouse models are cumbersome and not amenable to high-throughput analysis since they require de novo generation and characterization of genetically modified mice. Here we describe a new system for lineage-restricted expression of transgenes based on a retroviral vector incorporating a translational stop cassette flanked by loxP recombination sites. Conditional transgene expression in chimeric mice is achieved by retroviral infection and transplantation of hematopoietic stem cells (HSC) derived from transgenic mice expressing Cre-recombinase from a lineage-specific promoter. For validation, we directed expression of NPM-ALK, the fusion oncogene driving a subset of anaplastic large cell lymphoma (ALCL), to T-cells by infecting hematopoietic stem cells from Lck-Cre-transgenic mice with a retroviral construct containing the NPM-ALK cDNA preceded by a translational stop cassette. These mice developed T-cell lymphomas within 12-16 weeks, featuring increased expression of the ALCL hallmark antigen CD30 as well as other cytotoxic T-cell markers, similar to the human disease. The new model represents a versatile tool for the rapid analysis of gene function in a defined lineage or in a developmental stage in vivo.
Identifiants
pubmed: 31754210
doi: 10.1038/s41388-019-1058-1
pii: 10.1038/s41388-019-1058-1
doi:
Substances chimiques
Ki-1 Antigen
0
p80(NPM-ALK) protein
EC 2.7.1.-
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1904-1913Références
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