BALB/cJ mice exhibit considerable phenotypic differences with other BALB/c substrains. Some of these traits involve the liver, including persistent postnatal expression of genes that are normally expressed only in the fetal liver and reduced expression of major urinary proteins. These traits are due to a mutation that dramatically reduces expression of the gene encoding the transcription factor Zinc fingers and homeoboxes 2 (Zhx2). BALB/cJ mice also exhibit reduced serum lipid levels and resistance to atherosclerosis compared to other mouse strains when placed on a high-fat diet. This trait is also due, at least in part, to the Zhx2 mutation. Microarray analysis identified many genes affecting lipid homeostasis, including Lipoprotein lipase, that are dysregulated in BALB/cJ liver. This led us to investigate whether hepatic lipid levels would be different between BALB/cJ and BALB/c mice when placed on a normal chow or a high-fat chow diet. On the high-fat chow, BALB/cJ mice had increased weight gain, increased liver:body weight ratio, elevated hepatic lipid accumulation and markers of liver damage when compared to BALB/c mice. These traits in BALB/cJ mice were only partially reversed by a hepatocyte-specific Zhx2 transgene. These data indicate that Zhx2 reduces liver lipid levels and is hepatoprotective in mice on a high-fat diet, but the partial rescue by the Zhx2 transgene suggests a contribution by both parenchymal and non-parenchymal cells. A model to account for the cardiovascular and liver phenotype in mice with reduced Zhx2 levels is provided.

中文翻译：

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高脂饮食的BALB / c和BALB / cJ小鼠之间的肝脏大小和脂质含量差异部分归因于Zhx2。

BALB / cJ小鼠表现出与其他BALB / c亚株相当的表型差异。这些特征中的一些涉及肝脏，包括通常仅在胎儿肝脏中表达的基因的持续出生后表达和主要尿蛋白的表达降低。这些特征是由于突变，该突变显着降低了编码转录因子锌指和同源框2（Zhx2）的基因的表达。与其他高脂饮食小鼠品系相比，BALB / cJ小鼠还表现出降低的血脂水平和对动脉粥样硬化的抵抗力。此特征也至少部分是由于Zhx2突变引起的。微阵列分析鉴定了许多影响脂质稳态的基因，包括脂蛋白脂肪酶，这些基因在BALB / cJ肝脏中失调。这使我们研究了在正常饮食或高脂饮食下，BALB / cJ和BALB / c小鼠之间的肝脂质水平是否会有所不同。与BALB / c小鼠相比，在高脂食物上，BALB / cJ小鼠体重增加，肝：体重比增加，肝脂质蓄积增加和肝损伤标志物。BALB / cJ小鼠中的这些特征仅被肝细胞特异性Zhx2转基因部分逆转。这些数据表明，Zhx2可以降低高脂饮食小鼠的肝脏脂质水平，并且具有保肝作用，但是Zhx2转基因的部分拯救表明实质细胞和非实质细胞都有贡献。提供了一个模型来解释Zhx2水平降低的小鼠的心血管和肝脏表型。