LDLR基因沉默或敲除小鼠
- LDLR基因敲除小鼠日常喂养的高品质饲料
- 高脂血症的造模及相关研究
- 动脉粥样硬化模型的造模及相关研究
- 非酒精性脂肪肝模型及相关研究
- 肾纤维化(Renal Fibrosis)模型及相关研究
- 骨关节炎(osteoarthritis)模型及相关研究
- LDLR生理功能的研究
LDL受体基因沉默或敲除小鼠的特点
和日常喂养饲料和模型饲料须知
Regular Diet and Model Diet for LDLR-/- Mice
一、LDLR基因敲除小鼠的特点，决定了需要高质量的日常喂养饲料
载脂蛋白LDL受体（low density lipoprotein receptor，LDLR）广泛分布于肝脏、动脉壁平滑肌细胞、肾上腺皮质细胞、血管内皮细胞、淋巴细胞、单核细胞、巨噬细胞，各组织或细胞的LDL受体的表达和活性差别很大。毫无疑问，这种差别说明LDLR在不同组织和细胞的功能中发挥的作用和/或程度不同。
LDLR是细胞表面受体，在缺失（缺乏）后，血浆胆固醇不能被细胞摄入。因此，LDL受体敲除后后，最为明显的改变是血浆胆固醇升高，具有3个特点：
（1）在不含胆固醇的普通饲料喂养期间，血浆胆固醇大约是C57小鼠的2倍左右（200 mg/dL），这是内源性胆固醇升高，并且随着年龄的增大而缓慢升高。
（2）如果日常喂养的饲料中含有胆固醇，血浆胆固醇升高，这使得动物血浆胆固醇累积性升高（随着喂养时间的延伸，血浆胆固醇越来越高。
（3）如果日常喂养的是饲料中没有胆固醇，但脂肪较高，或者脂肪脂肪酸比例不合理（尤其是饱和脂肪酸过高），或者含有某些动物蛋白，可以升高血浆胆固醇（内源性胆固醇）。
因此，LDLR基因缺失后，喂养LDLR-KO小鼠的普通饲料质量非常关键。建议采用代码为LAD0011的专用饲料，详细情况，请点击：LAD0011介绍：脂蛋白代谢及其相关的基因工程大鼠和小鼠的日常喂养饲料。
LAD0011号大鼠小鼠普通饲料
注：LAD0011的原料选择与Harlan公司2018号普通饲料相当。
二、LDLR基因敲除小鼠的特点决定的多种疾病的发生和发展
由于LDLR-KO小鼠中LDLR的缺失，而LDLR受体生理性分布和功能很广，因此，LDLR-KO小鼠可用于与脂蛋白代谢或者转运异常相关的多种疾病的复制或造模。例如，除了最常用的高脂血症造模及相关研究，动脉粥样硬化模型的造模及相关研究 非酒精性脂肪肝模型及相关研究，肾脏纤维化模型及相关研究，骨关节炎(osteoarthritis)模型及相关研究，等等。
也正因为如此，当进行一种疾病的造模时，很可能同时发生了其他组织或器官的异常，从而干扰所进行的研究。因此，最为关键的是谨慎选择模型饲料和重视模型饲料的质量，在进行研究的过程中以及对研究结果进行分析时要尽量避免”只见树木，不见森林“。
三、LDLR基因敲除小鼠的特点决定的模型饲料选择要求
LDLR-KO小鼠最明显的特点是除了对饲料中胆固醇敏感，对饲料的脂肪含量和脂肪类型极其敏感。因此，要特别注意：
1.LDLR基因敲除小鼠用于研究肝脏外其他器官或组织的研究或疾病造模时的注意点
LDLR-KO小鼠对脂肪的敏感最主要体现在肝脏，容易形成脂肪肝等异常。因此，如果不是进行脂肪肝模型的造模，或者不是研究肝脏脂肪代谢以及脂肪对胆固醇代谢的关系，应当特别注意模型饲料中脂肪含量的控制和脂肪类型的选择，以避免脂肪肝形成或者减轻脂肪肝对研究结果的影响。
例如，如果研究血管内皮损伤或者动脉粥样硬化模型的造模及相关研究，如果模型饲料脂肪含量过高，这可能伴有明显的脂肪肝甚至可能脂肪肝的严重程度超过动脉粥样硬化的程度。正是这样的原因，你在“LDL受体基因敲除(LDLR-/-)小鼠动脉粥样硬化模型高脂肪高胆固醇模型饲料”或者“ "LDLR基因敲除(沉默）小鼠高脂血症模型饲料和造模方法”中可以看到，脂肪含量都不是很高。
2.LDLR基因敲除小鼠不同性别和造模时间的效应
LDLR-KO小鼠是否出现所需要的效应，与动物的性别和喂养造模时间有关。性别不同，对模型饲料的反应性有差异。除了高胆固醇血症、免疫功能异常等，其他绝大多数疾病的模型所需要的喂养时间都比较长，而不同疾病出现的时间和发展的程度有差别。因此，需要重视喂养时间的确定，必要时可以采取跟踪的方法了解模型的程度。
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