Ugt8a-KO Mouse

Ugt8a, also known as UDP-galactose:ceramide galactosyltransferase, is an enzyme involved in the synthesis of glycolipids, specifically galactosylceramides and related lipids. These lipids play crucial roles in various biological processes, such as myelination in the central nervous system (CNS) and are relevant to lipid metabolism pathways [5,6].

In male mice, integrated analysis of the kidney transcriptome identified Ugt8a as a potential enzyme responsible for male-specific glycolipid biosynthesis in vivo, which may be related to sex-dependency in kidney diseases. Inhibiting UGT8 (presumably Ugt8a) reduced the levels of certain glycolipids and inflammatory cytokines in the kidney [1]. In a study on Sandhoff disease in mice, the expression of Ugt8a was explored at different ages, but no significant differences in its expression levels related to myelination were found [2]. In the context of multiple sclerosis animal models, Ugt8a was among the downregulated mutual genes, suggesting its potential role in the pathogenesis [3]. In a mouse model of amyotrophic lateral sclerosis, a correlation was found between disease severity and the expression of Ugt8a, with joint-analysis revealing its involvement in glycosphingolipid metabolism [4].

In conclusion, Ugt8a is important for glycolipid biosynthesis and is implicated in multiple disease-related processes, including kidney diseases, Sandhoff disease, multiple sclerosis, and amyotrophic lateral sclerosis. Studies using mouse models have been instrumental in uncovering these roles, providing insights into the underlying molecular mechanisms and potential therapeutic targets for these diseases.

References:

1. Tsugawa, Hiroshi, Ishihara, Tomoaki, Ogasa, Kota, Minoda, Aki, Arita, Makoto. 2024. A lipidome landscape of aging in mice. In Nature aging, 4, 709-726. doi:10.1038/s43587-024-00610-6. https://pubmed.ncbi.nlm.nih.gov/38609525/

2. Singh, Kshitiz, Quinville, Brianna M, Mitchell, Melissa, Chen, Zhilin, Walia, Jagdeep S. 2022. Gene Expression Profile in the Sandhoff Mouse Brain with Progression of Age. In Genes, 13, . doi:10.3390/genes13112020. https://pubmed.ncbi.nlm.nih.gov/36360256/

3. Rahmat-Zaie, Roya, Amini, Javad, Haddadi, Mohammad, Sanadgol, Nima, Zendedel, Adib. 2023. TNF-α/STAT1/CXCL10 mutual inflammatory axis that contributes to the pathogenesis of experimental models of multiple sclerosis: A promising signaling pathway for targeted therapies. In Cytokine, 168, 156235. doi:10.1016/j.cyto.2023.156235. https://pubmed.ncbi.nlm.nih.gov/37267677/

4. Henriques, Alexandre, Croixmarie, Vincent, Bouscary, Alexandra, Spedding, Michael, Loeffler, Jean-Philippe. 2018. Sphingolipid Metabolism Is Dysregulated at Transcriptomic and Metabolic Levels in the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis. In Frontiers in molecular neuroscience, 10, 433. doi:10.3389/fnmol.2017.00433. https://pubmed.ncbi.nlm.nih.gov/29354030/

5. Saadat, Laleh, Dupree, Jeffrey L, Kilkus, John, Dawson, Glyn, Popko, Brian. . Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice. In Glia, 58, 391-8. doi:10.1002/glia.20930. https://pubmed.ncbi.nlm.nih.gov/19705459/

6. Wasseff, Sameh K, Scherer, Steven S. 2015. Activated immune response in an inherited leukodystrophy disease caused by the loss of oligodendrocyte gap junctions. In Neurobiology of disease, 82, 86-98. doi:10.1016/j.nbd.2015.05.018. https://pubmed.ncbi.nlm.nih.gov/26051537/