Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet.
Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet.
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DOI：
10.1371/journal.pone.0232069
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Verkade HJ
中科院分区：
文献类型：
--
作者：
Ronda OAHO;van de Heijning BJM;de Bruin A;Thomas RE;Martini I;Koehorst M;Gerding A;Koster MH;Bloks VW;Jurdzinski A;Mulder NL;Havinga R;van der Beek EM;Reijngoud DJ;Kuipers F;Verkade HJ
小鼠模型经常用于研究人类疾病的机制。最近，我们观察到一个自发的双峰变化，在C57 BL/6 JOlaHsd小鼠的肝脏重量喂食半合成的饮食。我们现在的特点是自发变化的肝脏重量及其与肝脂质和胆汁酸（BA）代谢参数的关系。在雄性C57 BL/6 JOlaHsd小鼠从出生到出生后第70天（PN）喂食AIN-93 G，我们测量了血浆BA，脂质，极低密度脂蛋白（VLDL）-甘油三酯（TG）分泌和肝脏mRNA表达模式。在PN 21、PN 42、PN 63和PN 70处死小鼠。在PN 70时，肝脏重量分布为双峰。根据肝脏重量，小鼠可分为两个不重叠的组：0.6 SD 0.1 g（约三分之一的小鼠，小肝脏; SL）和1.0 SD 0.1 g（正常肝脏; NL; p<0.05）。肝组织学显示SL组脂肪变性程度、炎症评分、核分裂相和纤维化程度均高于NL组。SL中血浆BA浓度高14倍（p<0.001）。SL小鼠中的VLDL-TG分泌速率较低，无论是绝对的（-66%，p<0.001）还是校正肝脏重量后的（-44%，p<0.001）。后来具有SL表型的小鼠在PN 21 -28期间显示出较低的食物效率比，表明SL表型的原因存在于断奶时（PN 21）。我们的数据显示，大约三分之一的C57 BL/6 JOlaHsd小鼠喂养半合成饲料发展自发性肝病异常的组织学和参数的肝脂质，胆汁酸和脂蛋白代谢。涉及这种小鼠品系的半合成饮食的研究设计需要考虑SL表型。血脂可作为SL表型鉴定的标志物。
Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (-66%, p<0.001) and upon correction for liver weight (-44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.
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影响因子：
4.2
作者：
Derks, T. G. J.;Boer, T. S.;Reijngoud, D. -J.
通讯作者：
Reijngoud, D. -J.
影响因子：
6.5
作者：
Millar, JS;Cromley, DA;Billheimer, JT
通讯作者：
Billheimer, JT
影响因子：
29.4
作者：
Dimova, Lidiya G.;de Boer, Jan Freark;Tietge, Uwe J. F.
通讯作者：
Tietge, Uwe J. F.
DOI：
10.1152/ajpendo.00332.2001
发表时间：
2002-04-01
影响因子：
5.1
作者：
Burcelin, M;Crivelli, V;Thorens, B
通讯作者：
Thorens, B
影响因子：
6.5
作者：
Lionarons DA;Boyer JL;Cai SY
通讯作者：
Cai SY