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Further characterization of factor VIII-deficient mice created by gene
targeting: RNA and protein studies
L Bi, R Sarkar, T Naas, AM Lawler, J Pain, SL Shumaker, V Bedian and HH Kazazian
Department of Genetics, University of Pennsylvania School of Medicine,
Philadelphia 19104, USA.
Previously we created two strains of factor VIII-deficient mice by
insertion of a neo gene into (1) the 3' end of exon 16 and (2) exon 17 of
the factor VIII gene. Affected mice of both strains have no plasma factor
VIII activity, yet are healthy with no spontaneous bleeding. Factor
VIII-deficient females bred with affected males survive pregnancy and
delivery. We used reverse transcriptase-polymerase chain reaction of liver
RNA to characterize factor VIII mRNA processing. Factor VIII mRNA of the
exon 16 knockout strain contains neo sequences plus 17 bp of intron 16 due
to use of a cryptic donor site in intron 16. All factor VIII mRNA of the
exon 17 knockout strain lacks exon 17 and neo sequences. In skipping exon
17, the intron 16 donor site or a cryptic donor site 46 bp 3' to the intron
16 donor site are used. Thus, factor VIII deficiency in exon 16 knockout
mice is due to truncated protein, while in exon 17 knockout mice it is due
to either truncated or partially deleted protein. After immunizing exon 16
knockout mice with human recombinant factor VIII, two monoclonal antibodies
were obtained that recognize < 100 pg of mouse factor VIII light chain.
Assay of cryoprecipitate from the plasma of affected mice failed to show
factor VIII light chain.
Volume 88,
Issue 9,
pp. 3446-3450,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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