Abnormal ornithine decarboxylase activity in transgenic mice increases tumor formation and infertility
Abnormal ornithine decarboxylase activity in transgenic mice increases tumor formation and infertility
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DOI：
10.1016/s1357-2725(01)00014-0
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发表时间：
2001-05-01
影响因子：
4
通讯作者：
Hietala, OA
中科院分区：
文献类型：
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作者：
Kilpeläinen, PT;Saarimies, J;Hietala, OA
为了研究鸟氨酸脱羧酶转基因表达在转基因小鼠的整个生命周期中是否具有任何生理或病理作用，产生了在小鼠乳腺肿瘤病毒长末端重复序列（MMTV LTR）启动子控制下携带鸟氨酸脱羧酶cDNA作为转基因的转基因小鼠系。高频率的不育动物和幼崽的丢失使得纯合子小鼠的繁殖失败。然而，一群杂合转基因小鼠被跟踪了2年。在成年杂合子转基因小鼠中，与非转基因对照组相比，睾丸、精囊和包皮腺中的鸟氨酸脱羧酶活性显著增加。相反，在转基因小鼠的肾脏和前列腺中，鸟氨酸脱羧酶活性降低。在卵巢和乳腺中未发现鸟氨酸脱羧酶活性的显著变化，在心脏、脑、胰腺和肺中仅检测到鸟氨酸脱羧酶活性的中度变化。在转基因系成年动物（12只雄性和20只雌性）中发现的最常见异常是炎症过程，包括胰腺炎、肝炎、涎腺炎和肾盂肾炎。在8只动物中观察到自发性肿瘤，包括2例良性肿瘤（皮肤纤维瘤：1例肝血管瘤）和6例恶性肿瘤（淋巴瘤，1例肠癌和3例乳腺腺癌以及1例肺腺癌）。在17个非转基因对照组中未发现明显的病理变化。(C)2001爱思唯尔科技有限公司版权所有。
A transgenic mouse line carrying ornithine decarboxylase cDNA as the transgene under the control of a mouse mammary tumor virus long terminal repeat (MMTV LTR) promoter was generated in order to study whether ornithine decarboxylase transgene expression will have any physiological or pathological effect during the entire life of a transgenic mouse. The high frequency of infertile animals and the loss of pups made the breeding of homozygous mice unsuccessful. However, a colony of heterozygous transgenic mice was followed for 2 years. In adult heterozygous transgenic mice, ornithine decarboxylase activity was significantly increased in the testis, seminal vesicle and preputial gland when compared to non-transgenic controls. In contrast, ornithine decarboxylase activity was decreased in the kidney and prostate of transgenic mice. No significant changes in ornithine decarboxylase activity were found in the ovary and mammary gland and only moderate changes in ornithine decarboxylase activity were detected in the heart, brain, pancreas and lung. The most common abnormalities found in adult animals (12 males and 20 females) of the transgenic line were inflammatory processes, including pancreatitis, hepatitis, sialoadenitis and pyelonephritis. Spontaneous tumors were observed in eight animals, including two benign tumors tone dermatofibroma: one liver hemangioma) and six malignant tumors tone lymphoma, one intestinal and three mammary adenocarcinomas and one adenocarcinoma in the lung). No significant pathological changes were found in 17 nontransgenic controls. (C) 2001 Elsevier Science Ltd. All rights reserved.