ALTERED CIRCADIAN ACTIVITY RHYTHMS AND SLEEP IN MICE DEVOID OF PRION PROTEIN

There is a wealth of data supporting a central role for the prion prot ein (PrP) in the neurodegenerative prion diseases of both humans and o ther species(1), yet the normal function of PrP, which is expressed at the cell surface of neurons and glial cells(2,3), is unknown. It has been speculated that neuropathology may be due to loss of normal funct ion of PrP (ref. 4). Here we show that in mice devoid of PrP there is an alteration in both circadian activity rhythms and sleep patterns. T o our knowledge, this is the first null mutation that has been shown t o affect sleep regulation and our results indicate that the pathology of at least one of the inherited prion diseases, fatal familial insomn ia(5), where there is a profound alteration in sleep and the daily rhy thms of many hormones(6-10), may be related to the normal function of the prion protein.