GTF2I, encoding the general transcription factor II-I (TFII-I), is a ubiquitously expressed transcription factor that can positively or negatively regulate gene expression [3,4]. It has been implicated in multiple pathways related to neuronal development, immunologic processes, and hematopoiesis [3,4]. The gene is of particular importance in understanding neurodevelopmental and immunologic diseases, as well as certain malignancies [4]. Genetic models, such as knockout mouse models, have been instrumental in studying its functions.

In knockout (KO) and conditional knockout (CKO) mouse models, Gtf2i deletion in neurons led to abnormal mitochondrial morphology, disrupted mRNA related to mitochondrial fission and fusion, and altered autophagy/mitophagy protein expression, highlighting its role in neuronal mitochondrial function [2]. Transgenic mice with Gtf2i duplication recapitulated progenitor proliferation and neuronal differentiation defects alongside ASD-like behaviors, suggesting GTF2I dosage regulates neuronal differentiation and social behavior [1]. In a knock-in mouse model with the GTF2I L424H mutation, the mutation impaired thymic medulla development and caused thymoma formation in aged mice, revealing its role in thymic epithelial tumorigenesis [5].

In conclusion, GTF2I plays essential roles in neuronal development, mitochondrial regulation, and thymic epithelial cell function. The study of Gtf2i KO/CKO mouse models has significantly contributed to understanding its functions in neurodevelopmental disorders like Williams-Beuren syndrome and 7q11.23 microduplication syndrome, as well as in thymic epithelial tumors [1,2,5].