Subject(s)
Apolipoprotein A-I/genetics , Gene Expression , Liver/metabolism , 3T3 Cells , Animals , Cell Line , Gene Transfer Techniques , Genes, Bacterial , Genetic Vectors , HeLa Cells , Humans , Mice , Plasmids , Promoter Regions, Genetic , Rats , Rats, Wistar , Retroviridae/geneticsSubject(s)
Apolipoprotein A-I/genetics , Gene Transfer Techniques , Genes, Bacterial , Genetic Markers , Liver/metabolism , Animals , DNA/genetics , Humans , Mice , Mice, Inbred C57BL , RatsSubject(s)
Apolipoprotein A-I/genetics , Gene Expression Regulation , Cell Division , Cell Line, Transformed , Cytomegalovirus/genetics , Enhancer Elements, Genetic , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation/genetics , HeLa Cells , Humans , Immunohistochemistry , Promoter Regions, Genetic , RNA/genetics , RNA/metabolismABSTRACT
Two transgenic rabbits which carried human apolipoprotein A-1 (apo A-1) cDNA under mouse ribosomal protein L/32 promoter were obtained. The effectiveness of transgenosis was confirmed by DNA dot/blot and Southern blot hybridizations. Both transgenic animals had paralyses of fore or fore and high limbs. Electron microscopy demonstrated distinct degradative changes of those parts of spinal cord which were responsible for leg skeletal muscle innervation. RNA dot/blot hybridization showed transgene expression in liver and brain but not in kidney of adult transgenic animal. However, analysis of blood serum lipids and immunochemical determinations gave no indications of the presence of human apo A-1 in adult transgenic rabbit. The data obtained allow us to suggest that the observed pathology was due to interference of native and foreign protein products of apo A-1 gene expression in CNS in the course of embryo development. This suggestion was supported by results of in situ hybridization of 5- and 9-week human embryo sections with apo A-1 cDNA, showing effective expression of apo A-1 gene in neural cells of CNS. Results of transgenosis may be viewed as modeling of the neurological syndrome of human Tangier disease.
Subject(s)
Apolipoprotein A-I/genetics , DNA , Nervous System Diseases/genetics , Tangier Disease/genetics , Animals , Animals, Genetically Modified , Apolipoprotein A-I/metabolism , Chloramphenicol O-Acetyltransferase/genetics , Humans , Microscopy, Electron , Models, Neurological , Muscles/innervation , Muscles/metabolism , Muscles/ultrastructure , Nervous System Diseases/complications , Nucleic Acid Hybridization , Promoter Regions, Genetic , Rabbits , Tangier Disease/complications , Tissue DistributionABSTRACT
The inheritance of the MT-1sAg transgene (a gene of the major envelope polypeptide of human hepatitis B virus under the control of the metallothionein I gene promoter) and its expression in mouse liver cells have been studied. The Mendel inheritance of the transgene for three generations of mice was established. The analysis of transgenic mouse F2 chromosomal DNA by the Southern hybridization revealed the tandem copy insertion of the MT-1sAg plasmid. The expression of the transgene in liver cells, both with MT-1 promoter induction by Cd++ and without it, has been observed. The decrease in mouse liver cell parts containing viral protein HBsAg was observed as well as a reliable decrease in the share of mice with detectable MT-1sAg expression in the liver during the ontogenesis. The MT-1sAg-transgenic mice may be useful for studying the human chronic HBsAg state.
