Suppression of Conditional TDP-43 Transgene Expression Differentially Affects Early Cognitive and Social Phenotypes in TDP-43 Mice

This study was carried out in accordance with the recommendations of the National Animal Care and Use Committee of the University of Buenos Aires (CICUAL). The protocol was approved by the CICUAL. Mice were kept under a 12-h light/dark cycle, with controlled temperature (23 ± 2°C) and humidity (40–60%) and had ad libitum access to food and water. To produce hTDP-43 transgenic lines, as described previously (Igaz et al., 2011), pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings were injected with a vector containing hTDP-43-WT cDNA. Monogenic tetO-TDP-WT12 mice were bred to Camk2a-tTA mice (Mayford et al., 1996; Jackson Laboratory) generating non-transgenic, tTA monogenic, single tetO-TDP-43 transgenic mice (non-TDP-43 expressing control mice) and bigenic mice expressing hTDP-43-WT12 (hereinafter referred to as tTA/WT12). Mice were treated with 0.2 mg/ml Dox (Doxycycline Hyclate, sc-204734A, Santa Cruz Biotechnology) in drinking water to avoid prenatal and postnatal developmental effects of transgene expression. hTDP-43 expression was induced by switching mice to regular drinking water (without Dox) at weaning (postnatal day 28). Mice were analyzed at different time points (Figure 1A). FIGURE 1 Figure 1. TDP-43 expression pattern in inducible TDP-43-WT transgenic mice. (A) Experimental design: transgene expression was inactive until postnatal day 28 by treatment with Dox. Fo...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research