Authors
Masaaki Kuwajima, Olga I Ostrovskaya, Lyndsey M Kirk, Ashley Alario, Weiling Yin, Sonia Singh, Anna Xaymongkhol, Adrienne Li, Ella Prasad, Kristen M Harris
Published in
PloS one. Volume 21. Issue 9. Pages e0355625. Epub Sep 03, 2026.
Abstract
The actin-binding protein synaptopodin (Synpo) regulates the cytoskeleton and organization of the endoplasmic reticulum, thereby amplifying intracellular Ca2+ signaling. Knockout (KO) mouse models have been used to study the role of Synpo in kidney and brain functions, where it supports stress fiber formation, as well as long-term potentiation (LTP) and learning, respectively. Here, we generated Synpo KO rats using CRISPR-Cas9, and show they are viable but have reduced body weight after postnatal days 35-45, along with shorter limb bone length. Their basal kidney function is normal into early adulthood. Serial section electron microscopy from Synpo KO rat hippocampus reveals the absence of the spine apparatus in dendrites and cisternal organelle in the axon initial segment (AIS), two Synpo-dependent specializations of smooth endoplasmic reticulum. The AIS in KO was still innervated by inhibitory synapses despite the total loss of the cisternal organelle. Synpo KO rats also showed reduced LTP. Previously unknown KO effect of Synpo on body stature could have an inadvertent impact on behavioral outcomes. Furthermore, rats have a well-defined developmental onset of LTP, compared to the variable onset of LTP in mice. This, combined with known species differences in behavior, makes our KO rat model a valuable resource for assessing the role of Synpo in development, learning, synaptic plasticity, and a wide range of other biological functions.
PMID:
42691043
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.
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