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A deletion mutation causes hemophilia B in Lhasa Apso dogs
AE Mauser, J Whitlark, KM Whitney and CD Lothrop
Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn
University, AL 36849, USA.
Hemophilia B is a bleeding disorder caused by a deficiency of clotting
factor IX (FIX). A colony of FIX deficient Lhasa Apso dogs has been
established and the molecular basis of hemophilia B has been determined.
The plasma factor IX levels were < 1% of normal canine levels in
affected dogs. A complex deletion mutation at nucleotides 772- 777 was
found when hepatocyte cDNA from a hemophilia B dog was sequenced. The
sequence was identical to the normal canine sequence except for a deletion
including nucleotides 772-776 and a C-->T transition at nucleotide 777.
The mutation results in mRNA instability and a premature termination codon
in the nucleotide sequence encoding the activation peptide. The mutation
was verified by sequencing genomic DNA from an FIX-deficient dog. A genetic
test for the detection of heterozygous animals was established using
heteroduplex analysis. Although hemophilia B has been described in many dog
breeds, this is only the second mutation to be sequenced. The Lhasa Apso
dog model should be valuable for evaluating novel strategies for treating
hemophilia B such as gene therapy.
Volume 88,
Issue 9,
pp. 3451-3455,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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