Klinefelter syndrome (KS, 47,XXY) is the most frequent male chromosomal aneuploidy resulting in a highly heterogeneous clinical phenotype associated with hormonal dysbalance, increased rate of co‐morbidities, and reduced lifespan. Two hallmarks of KS‐affecting testicular functions are consistently observed: Hypergonadotropic hypogonadism and germ cell (GC) loss resulting in infertility. Although KS is being studied for decades, the underlying mechanisms for the observed pathophysiology are still unclear. Due to ethical restrictions, studies in humans are limited, and consequently, suitable animal models are needed to address the consequences of a supernumerary X chromosome. Mouse strains with comparable aneuploidies have been generated and yielded highly relevant insights into KS. We briefly describe the establishment of the KS mouse models, summarize the knowledge gained by their use, compare findings from the mouse models to those obtained in clinical studies, and also reflect on limitations of the currently used models derived from the B6Ei.Lt‐Y* mouse strain, in which the Y chromosome is altered and its centromere position changed into a more distal location provoking meiotic non‐disjunction. Breeding such as XY* males to XX females, the target 41,XX^Y*, and 41,XXY males are generated. Here, we summarize features of both models but report in particular findings from our 41,XX^Y* mice including some novel data on Sertoli cell characteristics.

中文翻译：

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41，XXY *雄性小鼠：克氏综合征的动物模型。

Klinefelter综合征（KS，47，XXY）是最常见的男性染色体非整倍性，导致高度异质的临床表型与荷尔蒙失衡，合并症的发生率增加和寿命缩短。始终观察到KS影响睾丸功能的两个标志：促性腺激素性性腺功能减退和生殖细胞（GC）丧失导致不育。尽管对KS进行了数十年的研究，但所观察到的病理生理学的潜在机制仍不清楚。由于伦理上的限制，对人类的研究有限，因此，需要适当的动物模型来解决X染色体过多的后果。已经产生了具有可比非整倍性的小鼠品系，并对KS产生了高度相关的见解。我们简要描述KS鼠标模型的建立，总结使用它们所获得的知识，将小鼠模型的发现与临床研究中的发现进行比较，并反思当前使用的B6Ei.Lt-Y *小鼠品系的局限性，其中Y染色体发生了改变并且其着丝点位置改变为更远端的位置，从而引起减数分裂不分离。育种，例如XY *雄性到XX雌性，目标41，XX^Y *，并且生成41，XXY个男性。在这里，我们总结了这两种模型的特征，但特别报道了来自41，XX ^Y *小鼠的发现，包括有关Sertoli细胞特征的一些新数据。