Synaptopodin KO rat for assessing the dendritic spine apparatus and axonal cisternal organelle in synaptic plasticity, development, and behavior
- 1Department of Neuroscience and Center for Learning and Memory, The University of Texas at Austin, Austin, Texas, United States of America
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.
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BibTeX
@article{kuwajima2026synaptopodin,
title = {{Synaptopodin KO rat for assessing the dendritic spine apparatus and axonal cisternal organelle in synaptic plasticity, development, and behavior}},
author = {Masaaki Kuwajima and Olga I. Ostrovskaya and Lyndsey M. Kirk and Ashley Alario and Weiling Yin and Sonia Singh and Anna Xaymongkhol and Adrienne Li and Ella Prasad and Kristen M. Harris},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0355625},
url = {https://doi.org/10.1371/journal.pone.0355625},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synaptopodin KO rat for assessing the dendritic spine apparatus and axonal cisternal organelle in synaptic plasticity, development, and behavior
AU - Masaaki Kuwajima
AU - Olga I. Ostrovskaya
AU - Lyndsey M. Kirk
AU - Ashley Alario
AU - Weiling Yin
AU - Sonia Singh
AU - Anna Xaymongkhol
AU - Adrienne Li
AU - Ella Prasad
AU - Kristen M. Harris
PY - 2026
DA - 2026/09/03
JO - PLOS One
DO - 10.1371/journal.pone.0355625
UR - https://doi.org/10.1371/journal.pone.0355625
AB - 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.
SN - 1932-6203
ER -