Schaible R H
Department of Medical Genetics, Indiana University School of Medicine, Indianapolis.
Neurofibromatosis. 1989;2(3):138-51.
The yellow-nonyellow pattern of the tortoiseshell guinea pig is presented as a model for the distribution of mutant and nonmutant neural-crest cells in von Recklinghausen neurofibromatosis (NF-1). The following hypotheses are offered to explain the developmental genetics of the variable phenotype. (1) The gene for NF-1 is somatically unstable; reverse somatic mutation occurs at a high frequency among the stem cells of clones of neural-crest cells in all affected individuals. (2) The normal reverted cells suppress the proliferation of residual mutant cells when both types are in close proximity. (3) At puberty, proliferation of normal cells decelerates, but proliferation in islands of residual mutant cells accelerates and results in the development of neurofibromas. (4) Plexiform neurofibromas occur when reverse mutation fails to occur or takes place relatively late within a large clonal population of mutant cells.
玳瑁色豚鼠的黄-非黄毛色模式被用作冯·雷克林豪森神经纤维瘤病（NF-1）中突变和非突变神经嵴细胞分布的模型。以下假说是为了解释可变表型的发育遗传学。（1）NF-1基因在体细胞中不稳定；在所有受影响个体的神经嵴细胞克隆的干细胞中，反向体细胞突变高频发生。（2）当两种类型的细胞紧密相邻时，正常的回复细胞会抑制残余突变细胞的增殖。（3）在青春期，正常细胞的增殖减速，但残余突变细胞岛中的增殖加速，导致神经纤维瘤的发展。（4）当反向突变未能发生或在大量突变细胞克隆群体中发生相对较晚时，就会出现丛状神经纤维瘤。
