Studies on the Lethal Hyperlipidemia Spontaneouslly Occurred in the Mouse

我们研究了在INT菌株中出现的一种新的自发发生的突变体，这些突变体在出生后14天左右死亡。在这项研究中，我们试图证明死亡的原因和染色体位置的致病基因。结果如下：1。血液学研究：与正常小鼠相比，感染小鼠的血小板和白细胞数量分别增加1.8倍和1.6倍。白细胞增多提示患白血病。生化研究：与正常小鼠相比，血中三酰甘油（甘油三酯）和未酯化游离脂肪酸（FFA）浓度增加了7倍，游离胆固醇浓度增加了2.5倍。这个突变体是一种高甘油三酯血症。遗传研究：利用与MSM菌株的回交，对引起各种缺陷的基因进行了定位。结果表明，该基因为隐性基因，定位于Chr 17着丝粒56cM处。这个新的突变被证明是fsn（片状皮肤）突变的等位基因，其表型与int突变相似。根据国际小鼠命名委员会的规则，该突变被命名为fsn^<Jic>。组织病理学研究：在突变小鼠的肝脏中观察到由脂肪变性引起的大量空泡化。此外，肝脏、肾脏和脾脏中有核细胞数量的增加提示髓外造血的可能性。上述结果表明，fsn^<Jic>突变引起了典型的多效性，在各种器官和组织中表现出失败。在这项研究中，致病基因是遗传鉴定，但没有病原学做。

We studied a new spontaneouslly occurred mutants arisen in the INT strain, which die around 14 days after birth. In this study, we tried to demonstrate causes of death and chromosomal location of a causing gene. The results are as follows.1. Hematological studies : Comparing normal mice, the numbers of platelets and white blood cells in the affected mice were increased 1.8 and 1.6 times, respectively. Increase of WBC suggested that the affected mice suffered from leukemia.2. Biochemical studies : The concentrations of triacylglycerol (triglyceride) and unesterified free fatty acid (FFA) in bloods were increased 7 times and that of free cholesterol 2.5 times comapring those of normal mice. This mutant is a hypertriglyceridemia.3. Genetic studies : Mapping of the gene causing the various defects was carried out using backcrosses with the MSM strain. The results revealed that the gene is recessive and is mapped at 56cM from centromere of Chr 17. This new mutation was demonstrated to be an allele of the fsn (flaky skin) mutation with phenotypes similar to those of the int mutation. The int mutation was named fsn^<Jic> according to the rules of International Nomenclature Committee of the mouse.4. Histopathological studies : Massive vacuolation caused by steatosis (fatty degeneration) was observed in livers of the mutant mice. Also, an increase of the number of nucleated cells in livers, kidneys and spleens revealed a possibility of extramedullary hematopoiesis.The results described above demonstrated that the fsn^<Jic> mutation caused a typical pleiotropy displaying failures in various organs and tissues. In this study, the causal gene was genetically identified, but was not etiologically done.