Asnsd1, or asparagine synthetase domain containing 1, is conserved across many species with maximal expression in skeletal muscle [1]. Its exact function remains somewhat elusive, but it likely plays a role in metabolic interactions between skeletal muscle and adipose tissue, potentially involved in pathways related to muscle maintenance and fat metabolism [1]. Genetic models, such as knockout mice, have been crucial for studying Asnsd1's function.

In Asnsd1 -/- mice, a progressive degenerative myopathy occurs, leading to severe sarcopenia and myosteatosis [1]. These mice exhibit severe muscle weakness and a significantly increased body fat percentage, even on normal chow and high-fat diets [1]. Histologically, muscle is replaced by well-differentiated adipose tissue with minimal inflammation, fibrosis, and muscle regeneration [1]. The lack of lipotoxicity despite high body fat and low muscle mass suggests metabolic dysfunctions contribute to this phenotype [1]. In addition, a microprotein encoded by ASNSD1-uORF (ASDURF) is upregulated in childhood medulloblastoma, associated with MYC-family oncogenes, and promotes cancer cell survival through interaction with the prefoldin-like chaperone complex [2,3,4].

In conclusion, Asnsd1 is important for maintaining normal muscle function and may be involved in regulating the balance between muscle and adipose tissue. The Asnsd1 -/- mouse model has provided insights into the role of this gene in myopathy and myosteatosis, as well as the discovery of its microprotein's function in medulloblastoma. These findings highlight the significance of Asnsd1 in understanding muscle-adipose metabolic interactions and cancer-related processes.

References:

1. Vogel, Peter, Ding, Zhi-Ming, Read, Robert, Brommage, Robert, Powell, David R. 2020. Progressive Degenerative Myopathy and Myosteatosis in ASNSD1-Deficient Mice. In Veterinary pathology, 57, 723-735. doi:10.1177/0300985820939251. https://pubmed.ncbi.nlm.nih.gov/32638637/

2. Hofman, Damon A, Ruiz-Orera, Jorge, Yannuzzi, Ian, van Heesch, Sebastiaan, Prensner, John R. 2024. Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma. In Molecular cell, 84, 261-276.e18. doi:10.1016/j.molcel.2023.12.003. https://pubmed.ncbi.nlm.nih.gov/38176414/

3. Delaidelli, Alberto, Oliveira de Santis, Jessica, Sorensen, Poul H. . Actions speak louder than ORFs: A non-canonical microprotein promotes medulloblastoma oncogenesis. In Molecular cell, 84, 188-190. doi:10.1016/j.molcel.2023.12.027. https://pubmed.ncbi.nlm.nih.gov/38242097/

4. Hofman, Damon A, Ruiz-Orera, Jorge, Yannuzzi, Ian, van Heesch, Sebastiaan, Prensner, John R. 2023. Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.05.04.539399. https://pubmed.ncbi.nlm.nih.gov/37205492/