Gtdc1-KO Mouse

Gtdc1, glycosyltransferase-like domain containing 1, is a gene encoding a putative glycosyltransferase. Glycosyltransferases are involved in the synthesis of carbohydrate portions of glycoproteins, glycolipids, and proteoglycans. Gtdc1 has been implicated in various biological processes and diseases. Its expression is particularly enriched in the nervous system, suggesting a role in neurodevelopment [2,3].

In terms of disease-related findings, a de novo intragenic deletion of exons 5-6 of GTDC1 in a female individual was associated with a developmental encephalopathy characterized by epilepsy, severe intellectual disability, speech delay, microcephaly, and thin corpus callosum with facial dysmorphisms. RNA-seq analysis showed changes in glycine/serine and cytokine/chemokine signalling pathways, and increased glycine levels in the proband compared to controls, indicating that GTDC1 downregulation may be involved in neurodevelopmental impairment by altering glycine metabolism [2]. Also, disruption of GTDC1 in a patient with neurodevelopmental disorders, and in wild-type human neural progenitor cells and neurons, led to similar phenotypic defects, and a zebrafish model demonstrated its role in central nervous system development [3]. Additionally, prenatal prednisone exposure in rats decreased cartilage circRNomics, with circGtdc1 decreasing most significantly. This led to reduced chondrocyte proliferation and matrix synthesis, causing chondrodysplasia and increased susceptibility to osteoarthritis. Overexpression of circGtdc1 in vivo could ameliorate this condition [1].

In conclusion, Gtdc1 is crucial in neurodevelopment and cartilage-related biological processes. Research on Gtdc1 using gene-disrupted models, such as in patients with deletions and in zebrafish, has revealed its role in neurodevelopmental disorders and chondrodysplasia. Understanding Gtdc1 function provides insights into the mechanisms of these diseases, potentially guiding the development of new therapeutic strategies.