(10 pfus). The animals were subsequently necropsied and organs were evaluated 
for lacZ expressing cells by X-gal histochemistry from multiple blocks of tissue. Part 
of this study was an extensive analysis of tissue from testes. We have not detected 
lacZ-expressing cells in testes from any of these animals. 
IV.B.3. The effects of overexpression of CFTR 
IV.B.3.a. Overexpression of CFTR in transgenic mice 
Important safety concerns of this protocol relate to the consequences of 
ectopic and/or unregulated CFTR expression in the human lung. For example, will 
there be deleterious effects of CFTR expression in cells of the lung that do not 
normally express this gene? In collaboration with Dr. Jeff Whitsett, at the 
University of Cincinnati Medical Center, we established transgenic mouse lines that 
express human CFTR under the control of transcriptional elements derived from 
the human surfactant protein C(SP-C) gene (86). 
The hCFTR mRNA was expressed in lungs and testes: in the lung, we found 
hCFTR mRNA in bronchiolar and alveolar epithelial cells and CFTR protein in 
respiratory and epithelial cells. While the level of expression of hCFTR mRNA 
varied, hCFTR mRNA and protein were detected in pulmonary epithelial cells of 
several lines at high levels. Lung weight, morphology, somatic growth and 
reproductive capacity were not altered by expression hCFTR in lung and testes of 
the transgenics. Our findings suggest ectopic and unregulated expression of human 
CFTR in lung epithelial cells may not be deleterious. A copy of the paper 
describing this finding is provided in Appendix J. 
Recombinant DNA Research, Volume 17 
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