A deletion mutation causes hemophilia B in Lhasa Apso dogs.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Mauser AE,Whitlark J,Whitney KM,Lothrop CD Jr

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

3451-5

issue

9

eissn

0006-4971

issn

1528-0020

journal_volume

88

pub_type

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