UNIGE document Scientific Article
previous document  unige:39383  next document
add to browser collection
Title

Targeted mutation of zebrafish fga models human congenital afibrinogenemia

Authors
Published in Blood. 2014, vol. 123, no. 14, p. 2278-81
Abstract Mutations in the human fibrinogen genes can lead to the absence of circulating fibrinogen and cause congenital afibrinogenemia. This rare bleeding disorder is associated with a variable phenotype, which may be influenced by environment and genotype. Here, we present a zebrafish model of afibrinogenemia. We introduced targeted mutations into the zebrafish fga gene using zinc finger nuclease technology. Animals carrying 3 distinct frameshift mutations in fga were raised and bred to produce homozygous mutants. Using a panel of anti-zebrafish fibrinogen antibodies, fibrinogen was undetectable in plasma preparations from homozygous mutant fish. We observed hemorrhaging in fga mutants and reduced survival compared with control animals. This model will now serve in the search for afibrinogenemia modifying genes or agents and, to our knowledge, is the first transmissible zebrafish model of a defined human bleeding disorder.
Keywords Afibrinogenemia/congenital/genetics/pathologyAnimalsAnimals, Genetically ModifiedDisease Models, AnimalFibrinogen/geneticsHemorrhage/geneticsHumansLarvaMutagenesis, Site-DirectedPhenotypeZebrafish/genetics
Identifiers
PMID: 24553182
Full text
Article (Author postprint) (587 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Bases moléculaires des anomalies génétiques de l'hémostase (504)
Citation
(ISO format)
FISH, Richard, DI SANZA, Corinne, NEERMAN-ARBEZ, Marguerite. Targeted mutation of zebrafish fga models human congenital afibrinogenemia. In: Blood, 2014, vol. 123, n° 14, p. 2278-81. https://archive-ouverte.unige.ch/unige:39383

204 hits

4 downloads

Update

Deposited on : 2014-08-13

Export document
Format :
Citation style :