The targeting construct includes the signal sequence, first intron and propeptide of the mouse gene, the equivalent human cDNA and a neomycin cassette. Two site specific point mutations, T148A and R333Q were created in the human cDNA. The human cDNA is joined to the mouse gene at codons 6 and 7, such that the mouse expresses a missense mutant human protein, but does not express the mouse protein. ELISA analysis using specific human anti-F9 polyclonal antibodies detects human F9 in homozygous mice. (J:92964)