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402 TESTICULAR FAILURE AND LEARNING DEFICITS IN ADULT XXY MICE
  1. Y. H. Lue,
  2. J. D. Jentsch,
  3. C. Wang,
  4. A. P. Sinha-Hikim,
  5. W. A. Salameh,
  6. R. S. Swerdloff
  1. LA Biomed at Harbor-UCLA Medical Center, Torrance, 1Department of Psychology

Abstract

Klinefelter syndrome (XXY males) is the most common sex chromosome aneuploidy, occurring in about 1.2 per 1000 liveborn male births. XXY mice, an experimental murine model, were generated by utilizing a four-generation breeding scheme that involves the use of a structurally rearranged Y chromosome, Y*. Approximately 50% of the live born male offspring in the fourth generation were XXY mice identified by karyotyping performed on cultured fibroblasts from ear-clips. To characterize testicular phenotype, groups of 7 adult (2 or 3-month-old) XXY and their littermate XY mice were studied. There were no significant differences in body weight, but testis weights of adult XXY mice (22.50±1.03 mg) were markedly decreased compared with those of the controls (81.98±4.56 mg). Serum testosterone levels were significantly (P≤0.05) decreased in XXY mice (0.26±0.08 ng/ml) as compared with their XY littermates (0.57±0.08 ng/ml). The FSH levels in XXY mice (48.63±1.37 ng/ml) were significantly increased compared with those of XY (41.10±1.54 ng/ml) controls. However, LH levels were not significantly different between XXY (0.30±0.13 ng/ml) and XY (0.13±0.07 ng/ml) mice. Testicular histology of adult XXY mice showed small seminiferous tubules with varying degree of intraepithelial vacuolization and completely devoid of germ cells. Hypertrophy and hyperplasia of Leydig cells were observed in the interstitium. Interestingly, in one XXY mouse, we found a few seminiferous tubules containing zygotene and pachytene spermatocytes, but no round spermatids. Additional behavioral studies were conducted to determine whether XXY mice exhibited learning deficits. The acquisition of a Pavlovian tone-food association was assessed in groups of 7 adult (6 or 12-month-old) XXY and XY littermates. The rate of learning of the association was significantly slower in XXY mice, providing evidence for impaired medial temporal lobe function in XXY mice. We conclude that adult XXY mice have testicular failure and learning deficiencies, similar to its human counterpart, Klinefelter syndrome.

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