| First Author | Adão-Novaes J | Year | 2020 |
| Journal | Brain Res | Volume | 1727 |
| Pages | 146550 | PubMed ID | 31726043 |
| Mgi Jnum | J:283502 | Mgi Id | MGI:6386573 |
| Doi | 10.1016/j.brainres.2019.146550 | Citation | Adao-Novaes J, et al. (2020) Substrain-related dependence of Cu(I)-ATPase activity among prion protein-null mice. Brain Res 1727:146550 |
| abstractText | The prion protein (PrP(C)) binds copper and affects copper metabolism, albeit among a poorly understood functional landscape. Much of the data on physiological roles of PrP(C) were obtained in mice of mixed genetic background deficient of the PrP(C)-coding gene Prnp. This strategy is currently under scrutiny due to the flanking gene problem, in particular related with a polymorphism, typical of both the 129Sv and 129Ola mouse substrains, in the Sirpa gene located in the vicinity of Prnp. Here we report an investigation of biochemical properties of Cu(I)-ATPases as a function of genotype in two strains of PrP(C)-deficient mice. We found that both the brain and liver of Prnp-null mice of mixed B6;129Sv background had diminished activity, accompanied by increased catalytic phosphorylation of Cu(I)-ATPase, as compared with the respective wild-type animals. However, no such differences were found between Prnp-null and wild-type mice of a B10;129Ola background. Activity of Cu(I)-ATPase was strongly reduced in brain tissue from mice of 129Sv strain, when compared with wild-type either of B6;129Sv, and especially of mice of the B6 strain. No differences between wild-type and Prnp-null brain tissue were noted in the expression of either Atp7a or b genes, and RFLP analysis indicated that the Sirpa(129) polymorphism was present in both the B6;129Sv and B10;129Ola Prnp-null mouse colonies used in this study. The results suggest a novel substrain-dependent effect of 129Sv, but not 129Ola, genotype upon the regulation of the Cu(I)-ATPase catalytic cycle in Prnp-null mice, rather than either a Prnp-dependent, or a 129 strain-dependent effect. |
