Fig. 7: ASRGL1 silencing triggers death of motor neurons and TDP-43 proteinopathy in mice.
From: TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression
Adult female C57BL/6 mice received a stereotaxic injection to deliver 2 µl of viral solution (10e13 AAV9 viral particles/ml) in the motor cortex. Half of the mice (n = 5) received particles with a construct encoding 4 scrambled shRNAs and the other half (n = 5) received particles with a construct encoding 4 shRNAs against ASRGL1 (sequences in Supplementary Table 5). One month after the injection, brain sections were immunostained and analyzed by confocal microscopy. a Schematic representation of the injection site in the motor cortex (coordinates: 1.5 mm lateral, 1.1 mm anterior, 1.6 mm ventral) and the shRNA construct delivered within the AAV9 viral particles. b Representative images of brains sections from an ASRGL1-silenced mouse and a control stained for NeuN and CTIP2. c Comparison of NeuN+ cells (neurons) in the motor cortex of ASRGL1-silenced mice and controls (Unpaired T-test; Mean ± SEM). d Comparison of CTIP2+ cells (motor neurons) in the motor cortex of ASRGL1-silenced mice and controls (Mann–Whitney; Median (IQR)). e Brain section of an ASRGL1-silenced mouse showing cytoplasmic staining of TDP-43 (arrow heads), compared to a control mouse showing nuclear staining of TDP-43. f Percentage of cells showing cytoplasmic TDP-43 in ASRGL1-silenced mice and controls (Unpaired T-test; Mean ± SEM). All pairwise comparisons in the Figure were performed with two-sided tests. Source data are provided as a Source Data file.
