Smpd1-KO Mouse

Smpd1, which encodes sphingomyelin phosphodiesterase (ASM), is crucial as its product acid sphingomyelinase is involved in lipid metabolism. Deficient activity of ASM due to Smpd1 mutations is associated with Niemann-Pick Types A and B (NPA/B) diseases, autosomal recessive lysosomal storage disorders [1,4,5,6,7].

Mutations in Smpd1 are also associated with other diseases. In Parkinson's disease, certain Smpd1 mutations like p.L302P or p.fsP330 in the Ashkenazi Jewish cohort, and p.A487V in the Montreal/Montpellier cohort, were associated with the disease. Reduced acid-sphingomyelinase activity was linked to an earlier onset of PD. Also, Smpd1 knockout and knockdown led to increased α-synuclein levels in cells [3]. In β-thalassemia major patients, the Smpd1 gene c.132_143del, p.A46_L49del variant was detected, with associated differences in plasma chitotriosidase, ferritin, liver enzymes, and leukocyte acid sphingomyelinase levels [2].

In summary, Smpd1 is essential for normal lipid metabolism through the activity of acid sphingomyelinase it encodes. Its mutations are associated with Niemann-Pick Types A and B, Parkinson's disease, and β-thalassemia major. Research on Smpd1, including knockout/knockdown models, has provided insights into the role of Smpd1 in these disease conditions, helping to understand the underlying mechanisms and potentially guiding diagnosis and treatment [1-6].

References:

1. Zampieri, Stefania, Filocamo, Mirella, Pianta, Annalisa, Bembi, Bruno, Dardis, Andrea. 2015. SMPD1 Mutation Update: Database and Comprehensive Analysis of Published and Novel Variants. In Human mutation, 37, 139-47. doi:10.1002/humu.22923. https://pubmed.ncbi.nlm.nih.gov/26499107/

2. Dursun, Fadime Ersoy, Özen, Filiz. 2023. SMPD1 gene variants in patients with β-Thalassemia major. In Molecular biology reports, 50, 3355-3363. doi:10.1007/s11033-023-08275-x. https://pubmed.ncbi.nlm.nih.gov/36725747/

3. Alcalay, Roy N, Mallett, Victoria, Vanderperre, Benoît, Rouleau, Guy A, Gan-Or, Ziv. 2019. SMPD1 mutations, activity, and α-synuclein accumulation in Parkinson's disease. In Movement disorders : official journal of the Movement Disorder Society, 34, 526-535. doi:10.1002/mds.27642. https://pubmed.ncbi.nlm.nih.gov/30788890/

4. Wang, Ruisong, Qin, Ziyi, Huang, Long, Yang, Pinhong, Shi, Tieliu. 2023. SMPD1 expression profile and mutation landscape help decipher genotype-phenotype association and precision diagnosis for acid sphingomyelinase deficiency. In Hereditas, 160, 11. doi:10.1186/s41065-023-00272-1. https://pubmed.ncbi.nlm.nih.gov/36907956/

5. Schuchman, Edward H, Desnick, Robert J. 2016. Types A and B Niemann-Pick disease. In Molecular genetics and metabolism, 120, 27-33. doi:10.1016/j.ymgme.2016.12.008. https://pubmed.ncbi.nlm.nih.gov/28164782/

6. Molnar, Maria Judit, Szlepak, Tamas, Csürke, Ildikó, Erdős, Melinda, Dezsőfi, Antal. 2023. Case report: The spectrum of SMPD1 pathogenic variants in Hungary. In Frontiers in genetics, 14, 1158108. doi:10.3389/fgene.2023.1158108. https://pubmed.ncbi.nlm.nih.gov/37347058/

7. Pfrieger, Frank W. 2023. The Niemann-Pick type diseases - A synopsis of inborn errors in sphingolipid and cholesterol metabolism. In Progress in lipid research, 90, 101225. doi:10.1016/j.plipres.2023.101225. https://pubmed.ncbi.nlm.nih.gov/37003582/