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Studies on the Lethal Hyperlipidemia Spontaneouslly Occurred in the Mouse

小鼠自发性致死性高脂血症的研究

基本信息

批准号：
10480237
负责人：
KATOH Hideki
金额：
$ 4.74万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

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.

我们研究了在INT菌株中自发产生的一个新的突变体，它在出生后14天左右死亡。在这项研究中，我们试图证明死亡原因和导致基因的染色体定位。研究结果如下：1.研究结果。血液学检查：与正常小鼠相比，发病小鼠的血小板和白细胞数分别增加1.8倍和1.6倍。结论：1.WBC升高提示感染小鼠患白血病。生化研究：血液中甘油三酯和未酯化游离脂肪酸(FFA)浓度较正常小鼠增加7倍，游离胆固醇浓度增加2.5倍。该突变体为高甘油三酯血症。遗传学研究：利用与MSM菌株的回交，对导致各种缺陷的基因进行定位。结果表明，该基因是隐性的，位于Chr17着丝粒的56 cM处。该突变是FSN(鳞片状皮肤)突变的等位基因，其表型与INT突变相似。根据小鼠国际命名委员会的规则，将该INT突变命名为FSN^；JIC&gt；。组织病理学研究：在突变小鼠的肝脏中观察到由脂肪变性(脂肪变性)引起的大量空泡化。此外，肝、肾和脾中有核细胞数量的增加也表明了骨髓外造血的可能性。上述结果表明，FSN^；；JIC&gt；突变导致了典型的多效性，在各种器官和组织中表现为失败。在这项研究中，因果基因是从基因上确定的，但并不是病因学上的。