Sardh-KO Mouse

Sardh, or sarcosine dehydrogenase, is involved in the metabolism of the glycine-derivative sarcosine. It participates in the glycine production pathway, and is also linked to the purine cycle and one-carbon metabolism [1,4]. It has overall biological importance in processes like muscle function regulation, sex pheromone biosynthesis, and potentially in the immune system [1,3,2]. Genetic models can be valuable for studying its functions.

In Drosophila models, muscle-specific knockdown of Sardh leads to muscle dysfunction, ectopic lipid accumulation, and loss of the benefits of time-restricted feeding, suggesting its role in maintaining muscle function [1]. In male Bactrocera dorsalis, RNAi-mediated loss-of-function of Sardh decreases glycine, threonine (sex pheromone precursors), and sex pheromone contents, reducing male mating ability [3]. In children with sarcosinemia or in mice with Sardh deletion, formaldehyde deficiency due to the mutation of the mitochondrial Sardh gene leads to cognitive deficits, indicating its role in learning and memory [5].

In conclusion, Sardh plays essential roles in muscle function, sex pheromone biosynthesis, and learning and memory. Studies using gene knockout models in Drosophila, Bactrocera dorsalis, and mice have revealed its importance in these biological processes, providing insights into potential disease mechanisms related to muscle disorders, reproductive issues, and cognitive impairments.

References:

1. Livelo, Christopher, Guo, Yiming, Abou Daya, Farah, Panda, Satchidananda, Melkani, Girish C. 2023. Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models. In Nature communications, 14, 949. doi:10.1038/s41467-023-36474-4. https://pubmed.ncbi.nlm.nih.gov/36810287/

2. Lakshmikanth, Tadepally, Consiglio, Camila, Sardh, Fabian, Landegren, Nils, Brodin, Petter. 2024. Immune system adaptation during gender-affirming testosterone treatment. In Nature, 633, 155-164. doi:10.1038/s41586-024-07789-z. https://pubmed.ncbi.nlm.nih.gov/39232147/

3. Gui, Shiyu, Yuval, Boaz, Engl, Tobias, Lu, Yongyue, Cheng, Daifeng. 2023. Protein feeding mediates sex pheromone biosynthesis in an insect. In eLife, 12, . doi:10.7554/eLife.83469. https://pubmed.ncbi.nlm.nih.gov/36656757/

4. Green, Thomas, Chen, Xiaofei, Ryan, Stephen, Asch, Adam S, Ruiz-Echevarría, Maria J. 2013. TMEFF2 and SARDH cooperate to modulate one-carbon metabolism and invasion of prostate cancer cells. In The Prostate, 73, 1561-75. doi:10.1002/pros.22706. https://pubmed.ncbi.nlm.nih.gov/23824605/

5. Ai, Li, Tan, Tao, Tang, Yonghe, Cai, Xiang, Tong, Zhiqian. 2019. Endogenous formaldehyde is a memory-related molecule in mice and humans. In Communications biology, 2, 446. doi:10.1038/s42003-019-0694-x. https://pubmed.ncbi.nlm.nih.gov/31815201/