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PMID: 3029708 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of active human blood clotting factor IX in transgenic mice: use of a cDNA with complete mRNA sequence.

Nucleic acids research ·Vol. 15 ·No. 3 ·1987-02-11 ·Pages 871-84

Choo KH, Raphael K, McAdam W, Peterson MG

Abstract

Haemophilia B is a bleeding disorder caused by a functional deficiency of the clotting factor IX. A full length human factor IX complementary DNA clone containing all the natural mRNA sequences plus some flanking intron sequences was constructed with a metallothionein promoter and introduced into transgenic mice by microinjection into the pronuclei of fertilised eggs. The transgenic mice expressed high levels of messenger RNA, gamma-carboxylated and glycosylated protein, and biological clotting activity that are indistinguishable from normal human plasma factor IX. This study demonstrates the feasibility of expressing highly complex heterologous proteins in transgenic mice. It also provides the groundwork for the production of large amounts of human factor IX in larger transgenic livestock for therapeutic use, and the investigation of alternative genetic therapies for haemophilia B.

MeSH Terms
Animals Carcinoma, Hepatocellular/metabolism Cell Line Cloning, Molecular DNA/metabolism Enzyme-Linked Immunosorbent Assay Factor IX/genetics,isolation & purification Hemophilia A/genetics Humans Liver Neoplasms/metabolism Liver Neoplasms, Experimental/metabolism Mice Molecular Weight Plasmids RNA, Messenger/genetics Rats
Chemicals
RNA, Messenger Factor IX DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Choo K H
Raphael K
McAdam W
Peterson M G
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25 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/15.3.871
Published
1987-02-11
Pages
871-84
Language
English
Region
England
NLM ID
0411011
PMCID
PMC340495
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/15.3.871 PMC Full Text View journal details
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