Dhx37-KO Mouse

DHX37, an autosomal gene, encodes a helicase from the DExD/H-box family. It plays a crucial role in ribosome biogenesis in eukaryotes [1,2]. As ribosome biogenesis is fundamental for cell function, DHX37 is essential for normal cellular activities. Genetic models, such as gene knockout mouse models, could potentially be valuable in further exploring its functions.

DHX37 has been associated with various human disorders. Recurrent missense variants in DHX37 are linked to 46,XY gonadal dysgenesis, testicular regression syndrome (TRS), or anorchia, all non-syndromic forms of disorders/differences of sex development (DSD) [1]. These variants, affecting conserved amino acids in functional domains, may impact helicase function, yet how they cause DSD remains unclear [1]. Additionally, DHX37 variants are also associated with a complex congenital developmental syndrome (NEDBAVC) with features like microcephaly, global developmental delay, etc. [1]. In cancer research, higher DHX37 expression in hepatocellular carcinoma (HCC) is correlated with poor prognosis, and it may play roles in activating cell cycle, DNA repair, chemokine signaling pathways, and regulating immune response [3]. In CD8 T cells, Dhx37 knockout enhanced the efficacy of antigen-specific CD8 T cells against triple-negative breast cancer, with DHX37 suppressing effector functions, cytokine production, and T cell activation [4].

In summary, DHX37 is essential for ribosome biogenesis. Studies, including those from gene-knockout related models in some cases, have revealed its associations with multiple diseases. In the context of DSD, it appears to play a role in male sex development, especially in testis determination and maintenance [2]. In cancer, its overexpression in HCC is an independent risk factor for poor prognosis, suggesting it as a potential therapeutic target [3].

References:

1. McElreavey, Kenneth, Pailhoux, Eric, Bashamboo, Anu. 2022. DHX37 and 46,XY DSD: A New Ribosomopathy? In Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation, 16, 194-206. doi:10.1159/000522004. https://pubmed.ncbi.nlm.nih.gov/35835064/

2. de Oliveira, Felipe Rodrigues, Guaragna, Mara Sanches, Maciel-Guerra, Andréa Trevas, Guerra-Junior, Gil, Fabbri-Scallet, Helena. 2023. DHX37 and the Implications in Disorders of Sex Development: An Update Review. In Hormone research in paediatrics, 97, 433-444. doi:10.1159/000535969. https://pubmed.ncbi.nlm.nih.gov/38142677/

3. Liu, Nanbin, Zhang, Hailong, Zhang, Chunli, Li, Zongfang, Tian, Hongwei. 2023. DHX37 Is a Promising Prognostic Biomarker and a Therapeutic Target for Immunotherapy and Chemotherapy in HCC. In Cancers, 15, . doi:10.3390/cancers15215228. https://pubmed.ncbi.nlm.nih.gov/37958405/

4. Dong, Matthew B, Wang, Guangchuan, Chow, Ryan D, Herbst, Roy S, Chen, Sidi. . Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells. In Cell, 178, 1189-1204.e23. doi:10.1016/j.cell.2019.07.044. https://pubmed.ncbi.nlm.nih.gov/31442407/