DOI: 10.5061/dryad.1rr87
title: Data from: Impact of genetic reduction of NMNAT2 on chemotherapy-induced losses in cell viability in vitro and peripheral neuropathy in vivo

description: Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential
 neuronal maintenance factors postulated to preserve neuronal function and
 protect against axonal degeneration in various neurodegenerative disease
 states. We used in vitro and in vivo approaches to assess the impact of
 NMNAT2 reduction on cellular and physiological functions induced by
 treatment with a vinca alkaloid (vincristine) and a taxane-based
 (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice
 die at birth and cannot be used to probe functions of NMNAT2 in adult
 animals. Nonetheless, primary cortical cultures derived from NMNAT2-/-
 embryos showed reduced cell viability in response to either vincristine or
 paclitaxel treatment whereas those derived from NMNAT2 heterozygous
 (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced
 degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited
 a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative
 to wildtype (WT) mice with no change in levels of other NMNAT isoforms
 (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or
 microtubule associated protein-2 (MAP2) or neurofilament protein levels.
 We therefore compared the impact of NMNAT2 knockdown on the development
 and maintenance of chemotherapy-induced peripheral neuropathy induced by
 vincristine and paclitaxel treatment using NMNAT2+/- and WT mice.
 NMNAT2+/- did not differ from WT mice in either the development or
 maintenance of either mechanical or cold allodynia induced by either
 vincristine or paclitaxel treatment. Intradermal injection of capsaicin,
 the pungent ingredient in hot chili peppers, produced equivalent
 hypersensitivity in NMNAT2+/- and WT mice receiving vehicle in lieu of
 paclitaxel. Capsaicin-evoked hypersensitivity was enhanced by prior
 paclitaxel treatment but did not differ in either NMNAT2+/- or WT mice.
 Thus, capsaicin failed to unmask differences in nociceptive behaviors in
 either paclitaxel-treated or paclitaxel-untreated NMNAT2+/- and WT mice.
 Moreover, no differences in motor behavior were detected between genotypes
 in the rotarod test. Our studies do not preclude the possibility that
 complete knockout of NMNAT2 in a conditional knockout animal could unmask
 a role for NMNAT2 in protection against detrimental effects of
 chemotherapeutic treatment.
description: Vonfrey Acetone and
 RotaRod Data PaclitaxelContains raw data for
 the paclitaxel graphs and expiriments as well as rotarod data averages.
 Group A is the NMNAT2 +/- group and B is the wild-type
 group.CapsascinThe capsaicin spreadsheet contains raw data for each timepoint following capsaicin administration, as well as a tab for nocifensive behavior. The animals are the same as the paclitaxel spreadsheet.NMNAT Vonfrey Acetone Vincristine 9 29 14Contains raw data for the Vincristine graphs and experiments. Group A is the NMNAT2 +/- group and B is the wild-type group.MTT dataContains average output for three experiments for WT vs HET vs KO as well as the graph template for Figure 1.NMNATGraphPadThe primary graph file used to generate figures 2-5. Contains averages of each subject throughout the necessary timecourse (via the spreadsheets).DRGEXPDRG quantification data from western blots and NAD/NADH activity.