A monogenic senility syndrome segregating with longevity in mice.

We have found that around 2 years of age all surviving CBA T6/T6 mice develop hyperactivity and progressive weight loss, terminating in death, which is preceded in the males by priapism, persistent penile erection. As there is no genital lesion, the priapism is presumably of neurogenic origin, providing an invaluably specific sign of development of a neurological lesion. A loss of neurons, somewhere in the brain stem, not detectable without computerised, automated microscopy, not yet applied, is at present the best explanation for the occurrence of the syndrome. In maternally-derived F2 hybrids with the NZW and C57 BL/6 strains, the syndrome occurs exactly as in the CBAs, with a frequency of 25%, indicative of mediation by a single gene or gene cluster. The syndrome also occurs in the F1 hybrids, but with a 34-week delay, suggesting a delaying effect of either a halved CBA gene dosage, or of non-CBA genes. In NZW F2 hybrids the syndrome segregates with longevity (P < 0.001). The phenomenon provides an animal model for study of mechanisms of ageing and their relationship to senile neuropathies, such as Alzheimer's disease.