Hadrian Krzysztof, Szczerbowska-Boruchowska Magdalena, Surówka Artur, Ciepiela Olga, Litwin Tomasz, Przybyłkowski Adam
Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
Department of Medical Physics and Biophysics, AGH University of Science and Technology, Cracow, Poland.
Biometals. 2025 Feb;38(1):103-121. doi: 10.1007/s10534-024-00640-y. Epub 2024 Oct 4.
Toxic milk (txJ) is an autosomal recessive mutation in the Atp7b gene in the C3H/HeJ strain, observed at The Jackson Laboratory in Maine, USA. TxJ mice exhibit symptoms similar to those of human Wilson's disease (WD). The study aimed to verify organ involvement in a mouse model of WD. TxJ mice and control animals were sacrificed at 2, 4, 8, and 14 months of age. Total X-ray Fluorescence Spectroscopy (TXRF) was used to determine the elemental concentration in organs. Tissue chemical composition was measured by Fourier Transform Infrared Spectroscopy (FTIR). Additionally, hybrid mapping of FTIR and microXRF was performed. Elevated concentrations of Cu were observed in the liver, striatum, eye, heart, and duodenum of txJ mice across age groups. In the striatum of the oldest txJ mice, there was lower lipid content and a higher fraction of saturated fats. The secondary structure of striatum proteins was disturbed in txJ mice. In the livers of txJ mice, higher concentrations of saturated fats and disturbances in the secondary structure of proteins were observed. The concentration of neurofilaments was significantly higher in txJ serum. The distribution of Cu deposits in brains was uniform with no prevalence in any anatomic structure in either group, but significant protein structure changes were observed exclusively in the striatum of txJ. In this txJ animal model of WD, pathologic copper accumulation occurs in the duodenum, heart, and eye tissues. Increased copper concentration in the liver and brain results in increased saturated fat content and disturbances in secondary protein structure, leading to hepatic injury and neurodegeneration.
毒性牛奶（txJ）是C3H/HeJ品系中Atp7b基因的常染色体隐性突变，在美国缅因州的杰克逊实验室被发现。TxJ小鼠表现出与人类威尔逊病（WD）相似的症状。该研究旨在验证WD小鼠模型中器官的受累情况。TxJ小鼠和对照动物在2、4、8和14月龄时被处死。使用全X射线荧光光谱法（TXRF）测定器官中的元素浓度。通过傅里叶变换红外光谱法（FTIR）测量组织化学成分。此外，还进行了FTIR和微XRF的杂交图谱分析。在各年龄组的txJ小鼠的肝脏、纹状体、眼睛、心脏和十二指肠中均观察到铜浓度升高。在最老的txJ小鼠的纹状体中，脂质含量较低，饱和脂肪比例较高。txJ小鼠纹状体蛋白质的二级结构受到干扰。在txJ小鼠的肝脏中，观察到饱和脂肪浓度较高且蛋白质二级结构受到干扰。txJ血清中神经丝的浓度显著更高。两组中大脑中铜沉积物的分布均一，在任何解剖结构中均无优势，但仅在txJ的纹状体中观察到明显的蛋白质结构变化。在这个WD的txJ动物模型中，病理性铜积累发生在十二指肠、心脏和眼组织中。肝脏和大脑中铜浓度的增加导致饱和脂肪含量增加和蛋白质二级结构紊乱，从而导致肝损伤和神经退行性变。
