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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-5-28
pubmed:abstractText
We have tested the feasibility of producing large quantities of human serum albumin (HSA) in the milk of transgenic livestock by generating transgenic mice as a model system. The sheep beta-lactoglobulin (BLG) 5'-regulatory promoter sequences were used to support expression of BLG or HSA in transgenic mice. Transgenic animals generated from the entire BLG gene including 3, 5.5 or 10.8 kb of 5'-sequences demonstrated that 3 kb of 5'-sequences were sufficient to support high levels of expression of BLG, and that the longer 5'-sequences did not improve upon the levels of expression. As such, the 3 kb 5'-sequences were used to drive expression of HSA in BLG-HSA constructs. HSA was not detectably expressed in eight transgenic lines generated from a BLG-HSA construct containing the HSA cDNA. Two transgenic lines of 26 generated, using five different constructs, with an HSA minigene possessing the first intron expressed HSA in their milk. One of these expressed HSA at high levels (2.5 mg ml-1) and has stably transmitted this ability to its progeny. A high percentage of transgenic mouse lines (four of six) generated from a vector containing an HSA minigene possessing introns 1 and 2 expressed HSA in their milk at levels which ranged from 1 to 35 micrograms ml-1. In a similar trend, levels of expression of HSA by transfected tissue culture cells from BLG-HSA vectors containing an introduced SV40 enhancer were low with the HSA cDNA, increased with the HSA minigene with intron 1 and increased further with the minigene containing introns 1 and 2. This study demonstrates that high levels of HSA can be expressed in the milk of transgenic animals, that introns of the HSA gene play a role in its expression and that transfected cell lines may be used to quickly evaluate the relative expression efficiencies of various vector constructs intended for future transgenic evaluation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0962-8819
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-208
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:1284483-Animals, pubmed-meshheading:1284483-Antibodies, Monoclonal, pubmed-meshheading:1284483-Cloning, Molecular, pubmed-meshheading:1284483-DNA, pubmed-meshheading:1284483-Exons, pubmed-meshheading:1284483-Gene Expression, pubmed-meshheading:1284483-Gene Library, pubmed-meshheading:1284483-Genetic Vectors, pubmed-meshheading:1284483-Humans, pubmed-meshheading:1284483-Introns, pubmed-meshheading:1284483-Lactoglobulins, pubmed-meshheading:1284483-Liver, pubmed-meshheading:1284483-Mammary Glands, Animal, pubmed-meshheading:1284483-Mice, pubmed-meshheading:1284483-Mice, Transgenic, pubmed-meshheading:1284483-Milk, pubmed-meshheading:1284483-Milk Proteins, pubmed-meshheading:1284483-Polymerase Chain Reaction, pubmed-meshheading:1284483-Promoter Regions, Genetic, pubmed-meshheading:1284483-RNA, pubmed-meshheading:1284483-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:1284483-Restriction Mapping, pubmed-meshheading:1284483-Serum Albumin, pubmed-meshheading:1284483-Sheep, pubmed-meshheading:1284483-Transcription, Genetic
pubmed:year
1992
pubmed:articleTitle
Expression of human serum albumin in the milk of transgenic mice.
pubmed:affiliation
Institute of Animal Science, ARO, Volcani Center, Bet-Dagan, Israel.
pubmed:publicationType
Journal Article