Research Explained: Missense mutation in the activation segment of the kinase CK2 models Okur-Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse

Authors: Jose M. Cruz-Gamero, Demetra Ballardin, Barbara Lecis, Chun-Lei Zhang, Laetitia Cobret, Alexander Gast, Severine Morisset-Lopez, Rebecca Piskorowski, Dominique Langui, Joachim Jose, Guillaume Chevreux and Heike Rebholz

Publication Date: October 4, 2024

Research Explained By: Gabrielle Rushing, PhD, Chief Scientific Officer, CSNK2A1 Foundation

Link to article: Cruz Gamero Author MS

Research Explained Summary:

This publication characterizes the first mouse model of OCNDS. Researchers generated a mouse that has the K198R mutation in the alpha subunit of CK2, representing approximately 1/3rd of OCNDS patients. Results indicate that the mice have behavioral symptoms that resemble what is observed in humans, including an increase in repetitive movements, autism-like behaviors, memory deficits, and altered circadian activity that potentially represents sleep issues observed in humans. Notably, the K198R mice are smaller and weigh less than typical mice, potentially mirroring the postnatal short stature often seen in humans with OCNDS.

Further experiments demonstrated that the K198R mice have reduced CK2 activity and synapse formation in the hippocampus, a brain region important for learning and memory. Synapses are critical junctions where neurons communicate with one another and send messages. The authors found that K198R mice exhibit reduced synaptic plasticity, meaning the ability to respond to incoming messages to adjust the flow of information. This reduction suggests a possible mechanism for the behavioral and cognitive symptoms observed in OCNDS. There were no differences found in assays of motor abilities or social behavior. K198R mice did not exhibit spontaneous seizures but did show a reduced threshold (susceptibility) for seizures in assays where seizures where experimentally induced.



This mouse model represents a significant advancement in developing therapies for OCNDS. Its resemblance to the human condition allows researchers to use it as a valuable tool for preclinical therapeutic testing.