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Nucleic Acids Research, 1987, Vol. 15, No. 3 871-884
© 1987

Articles

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

K.H. Choo*, K. Raphael+, W. McAdam and M.G. Peterson

Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville 3052 Australia +CSIRO, Division of Animal Production, Great Western Highway, Blacktown 2148 Australia

*To whom correspondence should be addressed

Received December 19, 1986. Accepted January 13, 1987.

Haemophilia B is a bleeding disorder caused by a functional deficiency of the clotting factor IX (1). 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 livestook for therapeutic use, and the investigation of alternative genetic therapies for haemophilia B.


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