Gene-deletion experiments

Anaphylaxis in conjunction with inhibitor development has been described. Patients with hemophilia B with complete gene deletions have the greatest risk of anaphylaxis, with a minimum risk of 26%, whereas the risk in patients with null mutations was 2.4% and nearly zero for mis-sense mutations (13). Predisposing factors for the development of anaphylaxis, besides mutation type, are genetic predisposition and environmental experience, such as the type and frequency of factor IX product (13). 

The production of modified full-length derivatives of erythromycin has been achieved first by gene disruption experiments (see Section 12.3.1). Recent success in engineering new compounds via deletion of modules and domains, expression of single enzymes e.g., EryAI) and domain replacement have been described. 

Studies using synthetic peptides indicate that threonine is a better mannosyl acceptor in vitro, but the in vivo acceptor preferences of the individual Pmtps are not yet known. The existence of multiple Pmtps with differing acceptor specificities, coupled with the potential for these proteins to form heterodimers, may permit a wider range of peptide sequences to be recognized as substrates. However, deletion experiments with yeast PMT genes show that in some cases, a given Pmtp may be predominantly responsible for G-mannosylation of an individual protein, but that in others, several Pmtps have overlapping functions in G-mannosylation of a protein. 

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