Deletion of transcription factor Satb1 leads to disturbance in mice behavior through changes in the expression of genes-regulators of the excitive component of neurotransmission
Authors: Gavrish M. S. , Celis Suescun J. C. , Turovsky E. A. , Varlamova E. G. 
Published: May 2024

The transcription factor Satb1 exhibits widespread expression in multiple tissues and different regions of the brain. Notable levels of expression are observed in the neocortex, the nucleus of the diagonal band, the amygdala, and the tegmental area. In the ventral midbrain, Satb1-positive neurons are only found in a small portion of the substantia nigra, the ventral tegmental area, and the retrorubral field, and none were detected in the inferior colliculus. The transcription factor Satb1 is highly expressed in interneurons labeled as SST+, CR+, and NPY+, but not VIP+ interneurons. In mice with the Satb1 mutation, incomplete eye opening and a constriction reflex were observed.
Behavioral tests revealed that mice lacking Satb1 exhibited deficits in motor coordination, characterized by reduced mobility on flat bars and decreased grip strength on metal wires. In addition, these mice exhibited elevated levels of motor activity in novel environments and heightened anxiety in the light-dark test. Satb1-deficient males demonstrated proficiency in passive avoidance tests, while their female counterparts exhibited no significant difference in entrance time to the dark compartment between the reproduction and learning stages, indicating an impairment in the process of conditioned response formation.
To investigate the expression patterns of genes encoding vital protein kinases and proteins associated with neurotransmission, we extracted total RNA from the cerebral cortex of adult males with an incomplete deletion of Satb1. Real-time PCR analysis was conducted, which revealed a higher expression level of the pik3ca, pik3cb, and pic3cg genes responsible for phosphoinositide-3-kinase isoforms in Satb1-deficient mice compared to wild-type mice. The expression levels of genes encoding protein kinase C (Prkce and Prkcg) as well as Ca2+/calmodulin-dependent protein kinase II (Camk2) were lower in comparison to wild-type mice. Satb1-deficient mice displayed notably higher expression levels of genes encoding NMDA receptor subunits (Grin1, Grin2a, and Grin2b), whereas the expression of Gria1 (encoding the Glua2 subunit of AMPA receptors responsible for Ca2+ receptor conductance) decreased. The influence on excitatory glutamate receptor expression can cause hyperexcitability in animals, particularly when inhibitory neurotransmission is suppressed due to decreased Gabra1 and Gad65/67 expression encoding the GABA(A) receptor and glutamate decarboxylase. In addition, the levels of expression for the Calb1, Calb2, and Pvalb genes responsible for encoding the calcium-binding proteins calbindin, calretinin, and parvalbumin decreased in comparison to the wild-type mice.
Thus, a correlation was found between behavioral disturbances and expression of genes that encode proteins related to brain development and neurotransmission after deleting the Satb1 transcription factor. Satb1-deleted mice exhibited hyperexcitation and impaired motor activity due to impaired gene expression.