Human coxsackie adenovirus receptor (CAR) expression in transgenic mouse prostate tumors enhances adenoviral delivery of genes.

Abstract

BACKGROUND:

Transgenic mice that recapitulate the progression of human diseases are potentially useful models for testing the effectiveness of new therapeutic strategies. Their use in pre-clinical testing of adenovirally-delivered gene therapies, however, is limited because of restricted cell surface expression of Coxsackie adenovirus receptor (CAR) in mice.

METHODS:

To develop a more suitable transgenic mouse model for testing adenoviral-based gene therapies for prostate cancer, we generated prostate specific antigen/human CAR (PSA/hCAR) transgenic mice in which a chimeric enhancer/promoter sequence of the human PSA gene drives expression of a functional hCAR coding sequence.

RESULTS:

Expression of an adenovirally-delivered luciferase reporter gene in prostate tumor cells in bigenic mice (PSA/hCAR + TRAMP) was enhanced compared to the level in tumor cells lacking the PSA/hCAR transgene.

CONCLUSIONS:

Breeding PSA/hCAR mice to existing transgenic mouse models for prostate cancer (e.g., TRAMP) results in improved mouse models for testing adenovirally-delivered therapeutic genes.

• Authors: Yunhua Bao, Weidan Peng, Amy Verbitsky, Jiping Chen, Lily Wu, Katherine A Rauen, Janet A Sawicki
• Journal: The Prostate (Prostate) Vol. 64 Issue 4 Pg. 401-7 (Sep 01 2005) ISSN: 0270-4137 [Print] United States
• PMID: 15761871 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Chemical References

• CLMP protein, human
• CLMP protein, mouse
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Receptors, Virus

Topics

• Adenoviridae (genetics)
• Animals
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Disease Models, Animal
• Gene Expression
• Genetic Therapy (methods)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Prostatic Neoplasms (physiopathology, therapy)
• Receptors, Virus (genetics)