A highly conserved, multi-subunit TREX (Transcription-Export) complex mediates the export of mRNA from the cell nucleus to the cytoplasm in eukaryotic cells. We have implicated >40 variants in the X-linked THOC2 gene (encoding a subunit of TREX) in neurodevelopmental disorders (NDDs) with a varied phenotypic spectrum. However, there is a major gap in our understanding of the TREX function throughout the development, particularly the impact of THOC2 pathogenic patient variants on brain development leading to NDDs. We have addressed this question by generating a CRISPR/Cas-edited Thoc2 Exon37-38 deleted mouse model inspired by this variant we identified in a patient with intellectual disability, speech delay, hypotonia, and microcephaly. This, to the best of our knowledge, is the first Thoc2 partial loss of function (pLOF) mouse model of the TREX complex. We have confirmed the absence of off-target effects due to CRISPR/Cas editing by WGS and that Thoc2 Ex37-38 del male mice are smaller in size and weight (~15%) than their wild-type littermates; a phenotype similar to the patient. We have confirmed deletion of Ex37-38 sequences in Ex37-38 del male mice Thoc2 mRNAs and that the Thoc2 protein in Ex37-38 del male mice cortices, eye, and lungs is smaller than the wild-type protein. Our studies showed altered neuronal morphology and migration kinetics in the Ex37-38 del male mouse primary cortical neuron in-vitro cultures. We have identified altered cell cycle kinetics and cell death phenomenon in neural stem cells from the Thoc2 Ex37-38 del E18.5 mouse brains. Our findings so far suggest that pLOF THOC2 variation perturbs the fundamental mRNA export pathway leading to altered cell function that, when in brain (very sensitive to subtle changes), leads to neurocognitive pathologies. Our ongoing investigations on Thoc2 Ex37-38 del mouse model will provide insights into the cellular and molecular perturbations that lead to THOC2/TREX-associated NDDs.