Effects of PrP Gene Ablation

Further, neurophysiological abnormalities, namely a reduction of slow afterhyperploarization (AHPs) evoked by trains of action potentials in the hippocampus of PrP null mice, including disrupted Ga +-activated K+ currents and abnormal intrinsic properties of GAl pyramidal cells, have been reported (Colling et al, 1995 Colling et al, 

This PrP null phenotype has subsequently been confirmed by another group (Herms et al, 1998). Also an alteration in circadian rhythms, as well as disturbance in sleep patterns, has been described in these knockout mice (Tobler et al., 1996). 

A third PrP knockout line (Sakaguchi et al, 1996) posed a conundrum in that these mice developed a severe cerebellar ataxia and Purkinje cell degeneration at about 70 weeks of age. Subsequent to these three knockout lines, two more PrP-deficient lines of mice have been generated that 

Because the mating approach is nonselective, any unidentified gene whose inadvertent disruption might be causing the ataxic phenotype will be rescued as well. 

When the ataxic Sakaguchi knockout mice were crossed with transgenic mice haboring a wild-type mouse PrP-A transgene designated Tg(MoPrP-A)4053/FVB, none of the positive Tg P)Prnp° ° presented with ataxia at more than 90 weeks of age (Nishida et al, 1999). The number and topography of Purkinje cells were preserved in all areas of the cerebellar cortex in the Tg(P)mice. The authors concluded that the successful rescue of the ataxic phenotype in the Ngsk Prnp° ° 

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