Reply to Altered Monoaminergic Systems and Depressive-like Behavior in Congenic Prion Protein Knock-out Mice
- Danielle Beckman‡,
- Luis E. Santos‡,
- Tatiana A. Americo‡,
- Jose H. Ledo§,
- Fernando G. de Mello‡ and
- Rafael Linden‡1
- ↵1E-mail: rlinden{at}biof.ufrj.br
This is a response to a letter by Nuvolone and Aguzzi (1).
Nuvolone and Aguzzi (1) ascribed to the effect of a 129-Sirpa polymorphism, a macrophage phenotype we had previously attributed to PrPC, and we acknowledge that comparisons of wild-type and Prnp-null mice are subject to the flanking gene problem, as are many other studies of genetically modified mice. However, our current suggestion of a PrPC-monoaminergic link, consistent with the scaffold hypothesis, additionally relies on the binding of PrPC to monoaminergic markers.
Indeed, inference that Beckman's data result from Sirpa polymorphisms is unlikely. Our Prnp-null mice differed from wild-type in forced swim (FST), tail suspension (TST), and novelty suppressed feeding tests, whereas a truncated SIRPα modulated FST, but not TST, probably due to FST properties not shared with TST and, also differing from our results (2), produced no change in dopamine levels (3). Moreover, the inconsistent relative performances of B6 and 129 mice in depression-related tests reviewed by Jacobson and Cryan (4) do not corroborate the attribution of results in B10.129/Ola Prnp-null mice to the 129-Sirpa polymorphism. Notably, ischemic damage is affected in opposite ways by either truncated SIRPα or B6.129Sv Prnp-KO (5, 6).
As for immune responses known to depend on SIRPα, neither the sensitivity of neutrophils to spontaneous or peroxide-induced killing, their recruitment in vivo, nor phagocytosis by primary microglia differed between wild-type and Prnp-null mice of our B10.129/Ola colony (7, 8), which encompasses >10 years of inbreeding and >24 generations. Further investigation is therefore required to explain this apparent lack of differential effects of 129/Ola Sirpa polymorphism, as well as possible consequences of other Prnp-flanking genes.
- © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
