Редактирование: SPTLC1 (раздел)

==Publications==

{{medline-entry
|title=Mutant [[SPTLC1]] dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16210380
|abstract=Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. [[SPTLC1]] encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in [[SPTLC1]] cause hereditary sensory and autonomic neuropathy (type I) (HSAN1), an adult onset, autosomal dominant neuropathy. HSAN1 patients have reduced SPT activity. Expression of mutant [[SPTLC1]] in yeast and mammalian cell cultures dominantly inhibits SPT activity. We created transgenic mouse lines that ubiquitously overexpress either wild-type ([[SPTLC1]](WT)) or mutant [[SPTLC1]] ([[SPTLC1]](C133W)). We report here that [[SPTLC1]](C133W) mice develop age-dependent weight loss and mild sensory and motor impairments. Aged [[SPTLC1]](C133W) mice lose large myelinated axons in the ventral root of the spinal cord and demonstrate myelin thinning. There is also a loss of large myelinated axons in the dorsal roots, although the unmyelinated fibers are preserved. In the dorsal root ganglia, IB4 staining is diminished, whereas expression of the injury-induced transcription factor [[ATF3]] is increased. These mice represent a novel mouse model of peripheral neuropathy and confirm the link between mutant SPT and neuronal dysfunction.
|mesh-terms=* Aging
* Animals
* Axons
* Behavior, Animal
* CHO Cells
* Cricetinae
* Cricetulus
* Female
* Genes, Dominant
* Hereditary Sensory and Autonomic Neuropathies
* Male
* Mice
* Mice, Transgenic
* Mutation
* Pancreas, Exocrine
* Serine C-Palmitoyltransferase
* Transfection

|full-text-url=https://sci-hub.do/10.1093/hmg/ddi380
}}
{{medline-entry
|title=Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/14990347
|abstract=Hereditary sensory neuropathy type I (HSN1) is a common degenerative disorder of peripheral sensory neurons. HSN1 is caused by mutations in the gene, encoding the long chain base 1 of serine palmitoyltransferase (SPT) [Nat. Genet. 27 (2001) 309]. Here, we show a 44% reduction of SPT activity in transformed lymphocytes from HSN1 patients with mutation T399G in the [[SPTLC1]] gene. However, the decrease in SPT activity had no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death (apoptosis and necrosis). The removal of extracellular sphingolipids did not affect viability of HSN1 cells. We also found no significant difference in whole blood counts, viability, and permeability to Triton X-100 of primary lymphocytes from HSN1 patients. These results suggest that, despite the inhibition of mutant allele, the activity of nonmutant allele of STP may be sufficient for adequate sphingolipid biosynthesis and cell viability. Therefore, the neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effect(s) of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal protein(s) as in other neurodegenerations.
|mesh-terms=* Acyltransferases
* Aging
* Amino Acid Sequence
* Blood Cell Count
* Cell Division
* Cell Membrane Permeability
* Cell Survival
* Cell Transformation, Viral
* Cells, Cultured
* Hereditary Sensory and Autonomic Neuropathies
* Humans
* Lymphocytes
* Molecular Sequence Data
* Mutation
* Serine C-Palmitoyltransferase
* Sphingolipids

|full-text-url=https://sci-hub.do/10.1016/j.bbadis.2003.12.005
}}