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Updated: Jan 31, 2026
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Published on: January 7, 2019
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Aberrant Somatosensory Processing and Connectivity in Mice Lacking Engrailed-2
Gabriele Chelini1, Valerio Zerbi2, Luca Cimino1
1Center for Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy.
Summary
Engrailed-2 (En2) deficient mice exhibit fear responses to tactile stimuli, similar to autism spectrum disorder (ASD) symptoms. Reduced sensory cortex connectivity and altered brain activity in En2-/- mice suggest impaired somatosensory processing is common in ASD-related gene mutations.
Area of Science:
- Neuroscience
- Genetics
- Autism Spectrum Disorder Research
Background:
- Tactile overreactivity and defensive behaviors are common in autism spectrum disorder (ASD).
- Somatosensory hypersensitivity is observed in mice lacking ASD-associated genes like Fragile X mental retardation protein 1 (Fmr1).
- Reduced functional connectivity in sensory cortical areas may serve as a biomarker for hypersensitivity in ASD models.
Purpose of the Study:
- To investigate whole-brain functional connectivity in Engrailed-2 knock-out (En2-/-) mice, which exhibit reduced Fmr1 expression and ASD-related anatomical defects.
- To assess behavioral responses to somatosensory stimuli in En2-/- mice.
- To explore the neural correlates of aberrant somatosensory processing in En2-/- mice.
Main Methods:
- Magnetic Resonance Imaging (MRI)-based resting-state functional connectivity analysis in adult En2-/- mice.
- Behavioral testing using the whisker nuisance test and a sensory maze.
- Measurement of neuronal activity using c-Fos immunohistochemistry in the primary somatosensory cortex and basolateral amygdala.
Main Results:
- En2-/- mice displayed significantly reduced functional connectivity in somatosensory-auditory/associative cortices and dorsal thalamus.
- En2-/- mice exhibited fear behavior in response to whisker stimulation, unlike wild-type (WT) littermates.
- Reduced neuronal activity in the primary somatosensory cortex and increased activity in the basolateral amygdala were observed in En2-/- mice during whisker stimulation.
Conclusions:
- Fearful responses to somatosensory stimuli in En2-/- mice are linked to reduced sensory region connectivity and altered cortical/amygdala activation.
- Impaired somatosensory signal processing appears to be a shared characteristic in mice with mutations in ASD-related genes.
- En2-/- mice serve as a valuable model for studying sensory processing deficits in autism spectrum disorder.
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