Miyawaki S, Mitsuoka S, Sakiyama T, Kitagawa T
J Hered. 1982 Jul-Aug;73(4):257-63. doi: 10.1093/oxfordjournals.jhered.a109635.
A new autosomal recessive gene causing sphingomyelinosis in mice is described. The name sphingomyelinosis is proposed for this mutant with the gene symbol spm. The disease syndrome caused by this gene has been diagnosed as an analogue of Niemann-Pick disease in humans. Affected mice cannot breed. They show neurological symptoms and weight loss beginning from around 7 weeks of age, and die at 12-14 weeks. By 8 weeks of age striking hepatosplenomegaly and marked enlargement of lymph nodes are present. Large areas of the liver and spleen are replaced by clusters of foam cells. Purkinje cells in the cerebellum are severely depleted. The contents of sphingomyelin and free cholesterol in the liver and spleen are markedly elevated. But the brain shows no obvious changes in lipid concentrations. Sphingomyelinase activity is reduced to about 30 percent that of the homozygous normal controls in the liver, 50 percent in the spleen and 70-80 percent in the brain. Heterozygotes are normal in both lipid concentrations and sphingomyelinase activity. The syndrome produced by spm is different in several ways from that produced by fm, which has been reported to cause sphingomyelinosis in mice.
本文描述了一种导致小鼠鞘磷脂沉积症的新常染色体隐性基因。提议将该突变体命名为鞘磷脂沉积症，基因符号为spm。该基因引起的疾病综合征已被诊断为人类尼曼-匹克病的类似物。患病小鼠无法繁殖。它们从大约7周龄开始出现神经症状和体重减轻，并在12 - 14周龄时死亡。到8周龄时，出现明显的肝脾肿大和淋巴结显著肿大。肝脏和脾脏的大片区域被泡沫细胞簇取代。小脑的浦肯野细胞严重减少。肝脏和脾脏中鞘磷脂和游离胆固醇的含量显著升高。但大脑脂质浓度无明显变化。肝脏中鞘磷脂酶活性降至纯合正常对照的约30%，脾脏中降至50%，大脑中降至70 - 80%。杂合子在脂质浓度和鞘磷脂酶活性方面均正常。spm产生的综合征在几个方面与已报道的导致小鼠鞘磷脂沉积症的fm产生的综合征不同。
