Cardiac and vascular functions of the zebrafish orthologues of the type I neurofibromatosis gene NFI.
Von Recklinghausen neurofibromatosis is a common autosomal dominant genetic disorder characterized by benign and malignant tumors of neural crest origin. Significant progress in understanding the pathophysiology of this disease has occurred in recent years, largely aided by the development of relevant animal models. Von Recklinghausen neurofibromatosis is caused by mutations in the NF1 gene, which encodes neurofibromin, a large protein that modulates the activity of Ras. Here, we describe the identification and characterization of zebrafish nf1a and nf1b, orthologues of NF1, and show neural crest and cardiovascular defects resulting from morpholino knockdown, including vascular and cardiac valvular abnormalities. Development of a zebrafish model of von Recklinghausen neurofibromatosis will allow for structure-function analysis and genetic screens in this tractable vertebrate system.
Padmanabhan
Arun
A
Department of Cell and Developmental Biology, Penn Cardiovascular Institute, and the Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lee
Jeong-Soo
JS
Ismat
Fraz A
FA
Lu
Min Min
MM
Lawson
Nathan D
ND
Kanki
John P
JP
Look
A Thomas
AT
Epstein
Jonathan A
JA
D000818:Animals; D001483:Base Sequence; D018376:Cardiovascular Abnormalities / Q000196:embryology / Q000235:genetics; D002320:Cardiovascular Physiological Phenomena / Q000235:genetics*; D004195:Disease Models, Animal; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D017403:In Situ Hybridization; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D010802:Phylogeny; D013045:Species Specificity; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000502:physiology*
D020319:Oligodeoxyribonucleotides, Antisense