Molecular Genetics and Gene Therapy for Metabolic Disorders 
lived for only a few weeks in the recipient ani- 
mals. However, when the hepatocytes were re- 
turned to the liver of mice by direct injection into 
the portal vein or the spleen, the cells incorpo- 
rated themselves into the liver parenchyma and 
lived fpr as long as the mice did. They also con- 
tinued to function as hepatocytes in the trans- 
planted animals. These exciting results should 
form the foundation for the curing of liver dis- 
orders in humans by gene therapy in the future. 
The investigation of the feasibility of gene ther- 
apy for PKU has been hampered by the lack of an 
animal model. Recently, the laboratory of Wil- 
liam Dove at the University of Wisconsin has re- 
ported the creation by chemical mutagenesis of a 
mouse that is deficient in PAH activity in the 
liver. Our initial experiments with these mice 
have shown that the PAH gene can indeed be 
transferred into their hepatocytes in culture and 
reconstitute fully the missing enzyme activity. 
This mouse model will be critically important for 
us to test the efficacy of our hepatic gene transfer 
and hepatocyte transplantation protocols for cor- 
rection of the hepatic deficiency. 
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