Gene L突變小鼠的特性

Abstract

Gene L的生理功能未明，而本篇研究主要利用實驗室已建立的gene L 突變鼠，探討其生理功能，由於gene L突變鼠的外觀、體重與繁殖能力正常，因此進行健康檢查，分析肝功能、腎功能、血球及血脂，檢驗項目包括突變鼠禁食六小時後血糖、三酸甘油脂、總膽固醇、低密度脂蛋白、高密度脂蛋白濃度以及胰島素和葡萄糖耐受性試驗。本研究發現，gene L突變鼠血清丙胺酸轉胺酶和天門冬胺酸轉胺酶正常，表示突變鼠肝臟無明顯損傷。全血球分析結果顯示，gene L突變鼠的血小板數量異常但促血小板生成素無變化，因此未來需更多實驗探討血小板上升原因。接著利用H&E染色觀察到突變鼠肝臟有部分大顆囊泡類型的脂肪變性，並以Oil red O染色確認脂肪堆積於部分肝臟。生化分析顯示，gene L突變鼠血清三酸甘油脂、總膽固醇、低密度脂蛋白和高密度脂蛋白的濃度比野生型對照組高，然而肝臟總三酸甘油脂和總膽固醇含量正常。結合組織病理學結果和血清脂肪含量上升，懷疑突變鼠有可能發展成第二型糖尿病，因此檢測血糖並進行葡萄糖或胰島素耐受性試驗。結果顯示gene L突變鼠禁食血糖與野生型對照組之間無差異，灌食葡萄糖耐受性試驗結果亦無異常，但注射胰島素三十分鐘後對低血糖的反應較快。綜合上述結果，gene L突變鼠的肝臟脂肪代謝異常，進而可能發展成非酒精性脂肪肝。

The physiological function of gene L remains unclear, so the gene L mutant mice were produced to investigate. The gene L mutant mice were fertile and grew normally, and then the biomarkers of liver function, renal function, blood and serum lipids in the gene L mutant mice were analyzed, including the fasting blood concentration of glucose, triglycerides, cholesterols, low density lipoproteins (LDLs), high density lipoproteins (HDLs) and the insulin resistance and glucose tolerance tests. The alanine transaminase (ALT) and aspartate transaminase (AST) in the gene L mutant mice were normal indicating they had no liver injury. According to the CBC results, the platelet count in the gene L mutant mice was higher than the wild-type mice, but the thrombopoietin level didn’t increase in mutant mice, so it needs further investigation. H&E stains of mutant mice liver showed they had slight macrovesicular steatosis, and then confirmed lipid accumulation in some part of mutant mice liver by Oil red O stain. The serum triglycerides, total cholesterols, LDLs and HDLs were higher in the gene L mutant mice with increased lipid droplets accumulated in the liver. However, the gene L mutant mice had the normal amount of liver triglycerides and cholesterol. The observations of histopathology and increased serum lipid levels suggested the gene L mutant mice had high risk in developing type 2 diabetic mellitus, so I measured the fasting blood glucose and performed glucose and insulin tolerance tests. The results demonstrated the gene L mutant mice had normal effect in oral glucose tolerance test, and improved in response to hypoglycemia after insulin challenges. These results suggested that the gene L mutant might cause the development of non-alcoholic fatty liver disease (NAFLD) through the alterations of hepatic lipid metabolism without inducing glucose intolerance.