TY - JOUR
T1 - Adult Camk2a gene reinstatement restores the learning and plasticity deficits of Camk2a knockout mice
AU - Rigter, Pomme M.F.
AU - Wallaard, Ilse
AU - Aghadavoud Jolfaei, Mehrnoush
AU - Kingma, Jenina
AU - Post, Laura
AU - Elgersma, Minetta
AU - Elgersma, Ype
AU - van Woerden, Geeske M.
N1 - ACKNOWLEDGMENTS
We would like to thank Maria Smit and Armando Schoonbrood for technical assistance. This research was
supported by the NWO-VIDI (016.Vidi.188.014 to GW).
Publisher Copyright: © 2022 The Author(s)
PY - 2022/11/18
Y1 - 2022/11/18
N2 - With the recent findings that mutations in the gene encoding the α-subunit of calcium/calmodulin-dependent protein kinase II (CAMK2A) causes a neurodevelopmental disorder (NDD), it is of great therapeutic relevance to know if there exists a critical developmental time window in which CAMK2A needs to be expressed for normal brain development, or whether expression of the protein at later stages is still beneficial to restore normal functioning. To answer this question, we generated an inducible Camk2a mouse model, which allows us to express CAMK2A at any desired time. Here, we show that adult expression of CAMK2A rescues the behavioral and electrophysiological phenotypes seen in the Camk2a knock-out mice, including spatial and conditional learning and synaptic plasticity. These results suggest that CAMK2A does not play a critical irreversible role in neurodevelopment, which is of importance for future therapies to treat CAMK2A-dependent disorders.
AB - With the recent findings that mutations in the gene encoding the α-subunit of calcium/calmodulin-dependent protein kinase II (CAMK2A) causes a neurodevelopmental disorder (NDD), it is of great therapeutic relevance to know if there exists a critical developmental time window in which CAMK2A needs to be expressed for normal brain development, or whether expression of the protein at later stages is still beneficial to restore normal functioning. To answer this question, we generated an inducible Camk2a mouse model, which allows us to express CAMK2A at any desired time. Here, we show that adult expression of CAMK2A rescues the behavioral and electrophysiological phenotypes seen in the Camk2a knock-out mice, including spatial and conditional learning and synaptic plasticity. These results suggest that CAMK2A does not play a critical irreversible role in neurodevelopment, which is of importance for future therapies to treat CAMK2A-dependent disorders.
UR - http://www.scopus.com/inward/record.url?scp=85140259609&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.105303
DO - 10.1016/j.isci.2022.105303
M3 - Article
C2 - 36304100
AN - SCOPUS:85140259609
VL - 25
JO - iScience
JF - iScience
IS - 11
M1 - 105303
ER -