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Cre-loxP chromosome engineering of a targeted deletion in the mouse corresponding to the 3p21.3 region of homozygous loss in human tumours

Oncogene volume 21, pages 4521–4529 (2002)Cite this article

Abstract

Chromosomal deletions are a common feature of epithelial tumours and when further defined by homozygous deletions, are often the location of tumour suppressor genes. Deletions within the short arm of chromosome 3 occur very frequently in human carcinomas: a minimal region of loss at 3p21.3 (the Luca) region has been defined by overlapping homozygous deletions in lung and breast cancer cell lines. Using a rapid strategy for Cre-loxP chromosome engineering, a deletion of approximately 370 kb was created in the mouse germline corresponding to the deleted region at 3p21.3. The deletion when homozygous is embryonic lethal. Heterozygotes develop normally despite being haplo-insufficient for twelve genes including the candidate tumour suppressor gene Rassf1. Because damage to 3p21.3 often occurs very early in the sequence of genetic changes that lead to malignancy, particularly in lung and breast cancer, further genetic damage to these mice will provide the opportunity to model multi-step tumorigenesis of these tumours.

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Acknowledgements

We thank Ms Lorraine Dobbie and Ms Diana Peddie for chimera generation, mouse breeding and genotyping; Dr Terence Rabbitts for the 129/Ola mouse lambda library; Drs Michael Lerman and Eric Lander for the BAC clone and Dr Lerman for human cDNA Luca clones. This work was funded by the award of a BBSRC project grant to AJH Smith (15/G05898) and an MRC programme grant to PH Rabbitts (G9703123).

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Author notes

  1. Karen A Johnstone

    Present address: Department of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, 32610, Florida, USA

Authors and Affiliations

  1. Centre for Genome Research, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh, EH9 3JQ, UK

    Andrew J H Smith, Melville Richardson & Karen A Johnstone

  2. Department of Oncology, University of Cambridge, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Jian Xian & Pamela H Rabbitts

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  1. Andrew J H Smith
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Correspondence to Andrew J H Smith or Pamela H Rabbitts.

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Smith, A., Xian, J., Richardson, M. et al. Cre-loxP chromosome engineering of a targeted deletion in the mouse corresponding to the 3p21.3 region of homozygous loss in human tumours. Oncogene 21, 4521–4529 (2002). https://doi.org/10.1038/sj.onc.1205530

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