Horinouchi K, Erlich S, Perl D P, Ferlinz K, Bisgaier C L, Sandhoff K, Desnick R J, Stewart C L, Schuchman E H
Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA.
Nat Genet. 1995 Jul;10(3):288-93. doi: 10.1038/ng0795-288.
Types A and B Niemann-Pick disease (NPD) result from the deficient activity of acid sphingomyelinase (ASM). An animal model of NPD has been created by gene targeting. In affected animals, the disease followed a severe, neurodegenerative course and death occurred by eight months of age. Analysis of these animals showed their tissues had no detectable ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marked deficiency of Purkinje cells was evident. Microscopic analysis revealed 'NPD cells' in reticuloendothelial organs and characteristic NPD lesions in the brain. Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis.
A型和B型尼曼-匹克病（NPD）是由于酸性鞘磷脂酶（ASM）活性不足所致。通过基因靶向技术创建了NPD动物模型。在受影响的动物中，疾病呈严重的神经退行性病程，8个月大时死亡。对这些动物的分析表明，它们的组织中未检测到ASM活性，肝脏和大脑中的血液胆固醇水平和鞘磷脂升高，小脑萎缩和浦肯野细胞明显缺乏。显微镜分析显示网状内皮器官中有“NPD细胞”，大脑中有典型的NPD病变。因此，ASM缺陷小鼠对于研究NPD的发病机制和治疗方法，以及研究ASM在信号转导和细胞凋亡中的作用具有重要价值。
