A novel conditional NPM-ALK-driven model of CD30+ T-cell lymphoma mediated by a translational stop cassette.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Shoumariyeh K,Schneider N,Poggio T,Veratti P,Ehrenfeld S,Redhaber DM,Khan R,Pfeifer D,Klingeberg C,Kreutmair S,Rudelius M,Quintanilla-Martinez L,Fend F,Illert AL,Duyster J,Miething C

doi

10.1038/s41388-019-1058-1

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

1904-1913

issue

9

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-1058-1

journal_volume

39

pub_type

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