Skip to main content
. Author manuscript; available in PMC: 2022 Jan 17.
Published in final edited form as: Sci Transl Med. 2021 Sep 15;13(611):eabe8455. doi: 10.1126/scitranslmed.abe8455

Fig. 2. Wfs1+ neurons in mouse EC layer II propagate human tau to hippocampal CA1.

Fig. 2.

AAV2/6-Flex-tdTomato as a control or AAV2/6-Flex-P301L human mutant tau was injected unilaterally into the medial EC (MEC) of Wfs1-Cre mice. (A) Shown is a representative parasagittal section of the MEC and hippocampal CA1 area of a Wfs1-Cre mouse brain injected with AAV2/6-Flex-tdTomato as a control, immunostained with anti-RFP antibody (red) and anti-Wfs1 antibody (green). Scale bars, 100 μm (n = 10 sections from 10 animals). (B and C) Shown is a representative parasagittal section of MEC and the hippocampal CA1 area of a Wfs1-Cre mouse brain injected with AAV2/6-Flex-P301L human mutant tau. Sections were immunostained with anti-human tau HT7 antibody (green) and anti-Wfs1 antibody (red) 4 weeks after MEC injection. Scale bars, 100 μm (n = 26 sections from 7 animals). (D) Quantification of HT7+ neurons in the hippocampal CA1 area and dentate gyrus (DG) of Wfs1-Cre mouse brain injected with AAV2/6-Flex-P301L human mutant tau and immunostained with anti-human tau HT7 antibody at 4 weeks after MEC injection [two-way ANOVA on repeated measures, brain region tau effect F(1,12) = 173.9 ****P < 0.0001; average: unpaired t test, t = 13.19, ****P < 0.0001, n = 7 animals]. (E) Shown is a representative parasagittal section of the hippocampal CA1 area of a Wfs1-Cre mouse brain injected with AAV2/6-Flex-P301L mutant tau. Sections were immunostained with anti-Tau13 antibody (green) or anti-MC1 antibody (misfolded tau, green) or CP13 antibody (pSer202 tau, green) or AT8 antibody (pSer202/pThr205 tau, green) 4 weeks after MEC injection. Scale bars, 100 μm (n = 5 sections from 4 animals). (F) Quantification of human tau and pThr181 tau in EC and CA1-enriched hippocampal tissue of Wfs1-Cre mouse brain 4 weeks after MEC injection of AAV2/6-Flex-P301L mutant tau (unpaired t test, total tau EC: t = 6.335, CA1: t = 5.681, P181tau EC: t = 3.851, CA1: t = 3.639; **P < 0.01, ***P < 0.001, and ****P < 0.0001, n = 6 mice per group; table S2).