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Animal model for human liver disease: transgenic mice carrying viral and pathogenic genes
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Pharma cological Research . Vol. 22. Supplem ent 2.1990
Animal model for human liver disease: transgenic mice carrying viral and pathogenic genes. Sabina Perfumo. Laura Amicone. Stefano Colloca. Carlo Della RoecavLaura Pozzi e Marco Tripodi. Dipartimento di Biopatologia Umana. Sezione di Biologia Celliulare. -Sezione di Anatomia Patologica. Universita La Sapienza. Roma. Z allele of Human aHa I antitrypsin: we have established three transgenic mouse strains carrying an in vitro mutagenized 18Kb genomic fragment coding for hu man AIAT. The mutation is a GLU-> LYS342 substitution that is known to cause pulmonary emphysema and juvenile cirrhosis in man where the mutated protein is enzymatically inactive in lungs and accumulates intracellularly in liver . So far we detected a tissue specific gene expression in all transgenic strains. The plasma concentration of the protein is considerably low compared to the level detected in transgenic mice carrying the normal AIAT human allele, ~a l t h o u g h higher level of corresponding mRNA are found in Z allele carrying mice. Histological analysis is in progress. Hepatitis B virus X ORF: a large portion of human primary liver cancer is correlated to the chronically HBV carrier state, but the role, if any, of the viral proteins in transformation is not clear. Since ORF X has been shown in vitro to have a transactivation effect on various enhancers/promoters, we established two transgenic lines carrying the ORF X driven by its own promoter/enhancer .,Expression of the transgene has peen detected in various tissues and the histological analysis is in progress.
Laboratory animals genetically committed to liver pathologies will allow the study of the molecular mechanisms which directly trigger human pathologies and of the che mical, viral and genetic background factors which playa cooperative role. I043-66 I8/90/22II039Q--{) 1/$03.00/0
© 1990The Italian Pharmacological Society
Pharma cological Research . Vol. 22. Supplem ent 2.1990
Animal model for human liver disease: transgenic mice carrying viral and pathogenic genes. Sabina Perfumo. Laura Amicone. Stefano Colloca. Carlo Della RoecavLaura Pozzi e Marco Tripodi. Dipartimento di Biopatologia Umana. Sezione di Biologia Celliulare. -Sezione di Anatomia Patologica. Universita La Sapienza. Roma. Z allele of Human aHa I antitrypsin: we have established three transgenic mouse strains carrying an in vitro mutagenized 18Kb genomic fragment coding for hu man AIAT. The mutation is a GLU-> LYS342 substitution that is known to cause pulmonary emphysema and juvenile cirrhosis in man where the mutated protein is enzymatically inactive in lungs and accumulates intracellularly in liver . So far we detected a tissue specific gene expression in all transgenic strains. The plasma concentration of the protein is considerably low compared to the level detected in transgenic mice carrying the normal AIAT human allele, ~a l t h o u g h higher level of corresponding mRNA are found in Z allele carrying mice. Histological analysis is in progress. Hepatitis B virus X ORF: a large portion of human primary liver cancer is correlated to the chronically HBV carrier state, but the role, if any, of the viral proteins in transformation is not clear. Since ORF X has been shown in vitro to have a transactivation effect on various enhancers/promoters, we established two transgenic lines carrying the ORF X driven by its own promoter/enhancer .,Expression of the transgene has peen detected in various tissues and the histological analysis is in progress.
Laboratory animals genetically committed to liver pathologies will allow the study of the molecular mechanisms which directly trigger human pathologies and of the che mical, viral and genetic background factors which playa cooperative role. I043-66 I8/90/22II039Q--{) 1/$03.00/0
© 1990The Italian Pharmacological Society