Synaptopodin KO rat for assessing the dendritic spine apparatus and axonal cisternal organelle in synaptic plasticity, development, and behavior
Kuwajima, M.; Ostrovskaya, O. I.; Kirk, L. M.; Alario, A.; Yin, W.; Singh, S.; Xaymongkhol, A.; Li, A.; Prasad, E.; Harris, K. M.
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The actin-binding protein synaptopodin (Synpo) regulates the cytoskeleton and intracellular Ca2+ and is important for long-term potentiation (LTP) and learning. The inconsistent onset age for LTP in mice makes their Synpo knockout (KO) a suboptimal developmental model. Hence, we generated Synpo KO rats using CRISPR-Cas9. Synpo KO rats are viable with reduced body weight and bone length after postnatal days (P)35-P45. Their basal kidney function is normal. 3D reconstruction from electron microscopy reveals the absence of the Synpo-dependent dendritic spine apparatus and cisternal organelles in the axon initial segment (AIS), which may contribute to reduced LTP in the KO rat. Inhibitory synapses in the wild-type AIS appear preferentially clustered near cisternal organelles--a pattern disrupted in the KO, where synapses appear more uniformly distributed. The consistent developmental profile of LTP in the rat makes this KO a robust model to assess Synpo function in development, synaptic plasticity, and behavior. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/690444v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@e588c0org.highwire.dtl.DTLVardef@175302eorg.highwire.dtl.DTLVardef@ae3a81org.highwire.dtl.DTLVardef@82f0a1_HPS_FORMAT_FIGEXP M_FIG C_FIG
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