University of Texas System

Baylor College of Medicine

Rodney E Kellems

Michael R Blackburn

Surjit K Datta

Cho-Yau Yeung

The present invention relates to the production of adenosine deaminase (ADA) deficient mice and the use of such mice as an animal model for dysfunctions associated with elevated adenosine levels. Also, provided by the present invention are methods of treating dysfunctions associated with elevated adenosine levels and methods of screening compounds for pharmaceutical activity in the treatment of dysfunctions associated with elevated adenosine levels.

Adenosine deaminase deficient transgenic mice and methods for the use thereof

Disclosed are cultured mouse cells with amplified adenosine deaminase genes which greatly overproduce adenosine deaminase. The cells were isolated by growth in media containing alanosine, uridine, and a cytotoxic concentration of adenosine. Maximum enhancement of adenosine deaminase activity was achieved by also adding deoxycoformycin to the media and then serially increasing the deoxycoformycin concentration at 4 to 6 week intervals. Also disclosed is a cDNA homologous to mouse adenosine deaminase mRNA. The cDNA was produced by synthesis against RNA extracted from the cells containing amplified adenosine deaminase genes and then inserted into a bacterial plasmid. Multiple copies of the cDNA were produced by replication of the bacteria into which the plasmids were inserted.

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Houston, TX, United States of America

Rodney E Kellems