Reply to Jawaid et al.: Mitochondrial Dysfunction and Decrease in Body Weight of Transgenic Knock-in Mouse Model for TDP-43: the Question of Glucose?

Abstract

This is a response to a letter by Jawaid et al. (1). In their letter Jawaid et al. (1) refer to our recent paper on a TDP-43 transgenic knock-in (ki) mouse. The authors claim that Fig. 7 does not show differences in glucose levels of the animals and that an elevation of glucose levels would not be expected after mitochondrial dysfunction. In our measurements, glucose levels of TDP-43 ki animals were slightly elevated in ad libitum fed mice as compared with wild-type controls (ANOVA genotype-related p value was 0.04). In contrast, there was no significant difference in animals that were starved overnight. In these animals the tendency was to rather slightly lower levels. In my opinion, Fig. 7 clearly illustrates both these findings. Mitochondrial abnormalities have been found solely in the brain to date (e.g. not in spinal cords), and in a follow-up study using compound mutants of TDP-43 ki and another FTLD risk gene, we have just confirmed these findings. However, the reported observations concerning glucose and mitochondria are unrelated, as we underline in our paper (“Whether mitochondrial abnormality could explain the observed metabolic changes and altered body weight composition of hTDP-43A315T animals will be subject of future studies.”) (2).