Uncovering the Molecular Basis of X-linked Disorders 
code two additional proteins. The two extra mes- 
senger RNAs, termed factor Vlll-associated tran- 
scripts A and B, emanate from an intron, one of 
the noncoding regions of the factor VIII gene. 
The function of the gene is unknown, but the 
RNAs are produced at high levels in many differ- 
ent cell types, suggesting a "housekeeping" role. 
It is interesting to speculate that the A and B tran- 
seripts influence the expression of factor VIII and 
that mutations in them may in turn be responsible 
for some instances of hemophilia. 
Finally, we are attempting to create a hemophi- 
lic mouse. Genes on the X chromosome in hu- 
mans are located on the X in other mammals as 
well, and hemophilia has been recognized in 
male sheep, dogs, and cats. It would be prefera- 
ble, however, to use a mouse model for rapid 
testing of factor VIII products and for future gene 
therapy experiments. In progress are experi- 
ments to disrupt the normal mouse factor VIII 
gene, in hopes that male mice bearing the disrup- 
tion will have hemophilia. If successful, this ap- 
proach will be extended to create mouse models 
for other Xq28-linked disorders. 
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