TUMOR PREDISPOSITION IN MICE HETEROZYGOUS FOR A TARGETED MUTATION IN NF1
TUMOR PREDISPOSITION IN MICE HETEROZYGOUS FOR A TARGETED MUTATION IN NF1
复制标题
DOI：
10.1038/ng0794-353
复制
发表时间：
1994-07-01
期刊：
影响因子：
30.8
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
--
作者：
JACKS, T;SHIH, TS;WEINBERG, RA
人类1型神经纤维瘤病是由NF1基因突变等位基因遗传引起的显性疾病。为了研究NF1的功能，我们构建了一个携带小鼠同源种系突变的小鼠品系。杂合子动物不表现出人类疾病的典型症状，但极易形成各种类型的肿瘤，特别是褐细胞瘤（一种神经嵴源性肾上腺髓质的肿瘤）和髓性白血病，这两种肿瘤在人类NF1患者中发生的频率更高。野生型Nf1等位基因在大约一半的杂合动物肿瘤中丢失。此外，Nf1突变的纯合性导致心脏发育异常和妊娠中期胚胎死亡。
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 midgestational embryonic lethality.