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Tumour predisposition in mice heterozygous for a targeted mutation in Nf1.

Authors:
Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA
Affiliation:
Journal:
Nature genetics

Abstract

Human neurofibromatosis type 1 is a dominant disease caused by the inheritance of a mutant allele of the NF1 gene. In order to study NF1 function, we have constructed a mouse strain carrying a germline mutation in the murine homologue. Heterozygous animals do not exhibit the classical symptoms of the human disease, but are highly predisposed to the formation of various tumour types, notably phaeochomocytoma, a tumour of the neural crest-derived adrenal medulla, and myeloid leukaemia, both of which occur with increased frequency in human NF1 patients. The wild-type Nf1 allele is lost in approximately half of the tumours from heterozygous animals. In addition, homozygosity for the Nf1 mutation leads to abnormal cardiac development and mid-gestational embryonic lethality.

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