Yamamoto T, Iwasawa K, Tokoro T, Eto Y, Maekawa K
Department of Pediatrics, Jikei University, School of Medicine, Tokyo.
No To Hattatsu. 1994 Jul;26(4):318-22.
We found two Niemann-Pick disease model mouse species, NCTR-BALB/c mouse and SPM mouse. NCTR-BALB/c mouse is known as a model mouse of Niemann-Pick disease type C, because cholesterol esterification is deficient in fibroblasts. On the other hand, SPM mouse has been thought as a model of Niemann-Pick disease type A. However, we disclosed cholesterol esterification in fibroblasts from SPM mice is also deficient. It indicates that two model mice could be caused by a same genetic deficiency. To test if the genetic defect of those mice are located in the same gene, we made NCTR-BALB/c mouse heterozygotes mate with SPM mouse heterozygotes. The F1 mice are investigated by lipid analysis, lysosomal enzyme assay, cholesterol esterification ratio, and electron microscopic study. Eleven in 42 F1 mice (25%) got affected, and the clinically affected F1 mice had the biological and morphological abnormalities which are seen in SPM and NCTR-BALB/c mice. These data suggest that genetic defects in NCTR-BALB/c and SPM mice are located in the same gene.
我们发现了两种尼曼-匹克病模型小鼠，即NCTR-BALB/c小鼠和SPM小鼠。NCTR-BALB/c小鼠被认为是C型尼曼-匹克病的模型小鼠，因为其成纤维细胞中的胆固醇酯化存在缺陷。另一方面，SPM小鼠一直被认为是A型尼曼-匹克病的模型。然而，我们发现SPM小鼠成纤维细胞中的胆固醇酯化同样存在缺陷。这表明这两种模型小鼠可能是由相同的基因缺陷导致的。为了测试这些小鼠的基因缺陷是否位于同一个基因中，我们让NCTR-BALB/c小鼠杂合子与SPM小鼠杂合子交配。通过脂质分析、溶酶体酶测定、胆固醇酯化率和电子显微镜研究对F1代小鼠进行了检测。42只F1代小鼠中有11只（25%）受到影响，临床受影响的F1代小鼠出现了SPM和NCTR-BALB/c小鼠中所见的生物学和形态学异常。这些数据表明，NCTR-BALB/c小鼠和SPM小鼠的基因缺陷位于同一个基因中。
