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FVB/NCr小鼠的自发性垂体异常和乳腺增生:对小鼠模型的影响

Spontaneous pituitary abnormalities and mammary hyperplasia in FVB/NCr mice: implications for mouse modeling.

作者信息

Wakefield Lalage M, Thordarson Gudmundur, Nieto Ana I, Shyamala G, Galvez Jose J, Anver Miriam R, Cardiff Robert D

机构信息

Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA.

出版信息

Comp Med. 2003 Aug;53(4):424-32.

Abstract

The FVB/N mouse strain is widely used in the generation of transgenic mouse models. We have observed that mammary glands of wild-type virgin female FVB/NCr mice frequently have the morphologic and histologic appearance of a gland during pregnancy. By 13 months of age, the mammary glands of more than 40% of the mice examined had lobuloalveolar hyperplasia that was characterized by the presence of secretory alveoli and distended ducts apparently containing secretory material. The prevalence of this phenotype further increased with age. The mammary phenotype was highly correlated with the presence of proliferative, prolactin-secreting lesions in the pituitary gland. In mice aged 18 to 23 months, hyperplasia of the pars distalis was seen in 11 of 21 mice (52%), and a further 4 of 21 mice (19%) had pituitary adenomas. Pituitary hyperplasia was already evident in some mice as young as nine months. The pituitary phenotype was also associated with high prevalence (4/6 mice) of spontaneous mammary tumors in aged multiparous, but not virgin FVB/NCr mice. This high prevalence of pituitary abnormalities and their effects on the mammary gland have important consequences for the interpretation of new phenotypes generated in transgenic models using this mouse substrain.

摘要

FVB/N小鼠品系广泛用于转基因小鼠模型的构建。我们观察到,野生型未孕雌性FVB/NCr小鼠的乳腺在形态学和组织学上常常呈现出孕期腺体的外观。到13月龄时,超过40%接受检查的小鼠乳腺出现小叶腺泡增生,其特征为存在分泌性肺泡以及明显含有分泌物质的扩张导管。这种表型的发生率随年龄增长进一步升高。乳腺表型与垂体中增殖性、分泌催乳素的病变的存在高度相关。在18至23月龄的小鼠中,21只小鼠中有11只(52%)出现远侧部增生,另外21只小鼠中有4只(19%)患有垂体腺瘤。垂体增生在一些年仅9个月的小鼠中就已明显。垂体表型还与老龄经产FVB/NCr小鼠(而非未孕小鼠)中自发性乳腺肿瘤的高发生率(4/6小鼠)相关。垂体异常的这种高发生率及其对乳腺的影响对于使用该小鼠亚系的转基因模型中产生的新表型的解释具有重要意义。

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