41,XXY * male mice: An animal model for Klinefelter syndrome

Abstract

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.

Keywords: 41,XXY* mouse; Klinefelter syndrome; Sertoli cell; chromosomal imbalance; germ cell loss.