A.Cg-Sptssb^Tvrm122/PjnMmjax

Stock number: 031244
Product name: stellar
Strain synonyms: Sptssb^St
Research areas: Developmental Biology Research, Neurobiology Research, Sensorineural Research

Description

These ENU-induced Tvrm122 mice carry an H56L mutation in the Sptssb (serine palmitoyltransferase, small subunit B) gene. Mice homozygous and heterozygous for the mutation exhibit an increase in 20 carbon sphingoid long chain bases (C20 LCBs) resulting in neurodegeneration. This strain may be useful for studying the effect of bioactive sphingolipids in the brain and eye.

Detailed description

Sptssb (serine palmitoyltransferase, small subunit B) encodes the small beta subunit of serine palmitoyltransferase and is involved in sphingolipid biosynthesis. This ENU-induced mutation, Tvrm122, was identified as a histidine to leucine substitution at amino acid residue 56 (H56L). Mice heterozygous for Tvrm122 were initially identified by the appearance of shiny flecks in the fundus of the eye. This phenotype is more extreme in homozygotes. The flecks are the result of aberrant, hyperreflective membranes in the inner and outer plexiform layers. Homozygous mice exhibit early onset ataxia, reduced body weight, and often die by 10 weeks of age.

By two weeks of age, mice develop abnormal neurofilament H accumulation in the cerebellar white matter and the optic nerve, which consists of degenerating axons filled with electron dense material and vacuoles. Vacuolar structures are observed in the deep cerebellar nuclei, brainstem, midbrain, pontine nuclei, thalamus, and areas of the hypothalamus; in young mice (2 weeks) the structures are in close proximity to the endoplasmic reticulum. Vacuolar structures also are present in heterozygotes, but are much more sparse. In addition, there is an accumulation of ubiquitinated proteins on membranes. 18 carbon sphingoid long chain bases (C18 LCBs) are present in normal or slightly elevated numbers as compared to wild-type mice, however, C20 LCBs are increased by 2-3 fold in homozygotes and 1-fold in heterozygotes. The increase in C20 LCBs correlates with the severity of neurodegeneration in the brain. This strain may be useful for studying the effect of bioactive sphingolipids in the brain and eye.

Development

This mutation was identified in the G3 population derived from an ENU treated hybrid A.B6-Tyr⁺/J and C57BL/6J G3 ENU-induced mutant. Subsequently, the strain was maintained by at least six crosses to A.B6-Tyr⁺/J. Upon arrival, mice were bred to A/J for at least 1 generation to establish the colony. As a result, mice are segregating the albino allele. The mutation was identified as A to T at position 167 of the Sptssb (serine palmitoyltransferase, small subunit B) gene and is predicted to cause alter a histidine to leucine at amino acid 56 (H56L).

Allele

Symbol: Sptssb^Tvrm122
Name: translational vision research model 122
MGI accession ID: MGI:5689843
Generation method: Chemically induced (ENU)
Attributes: Constitutively active
Synonyms: Sptssb^St; Sptssb^Stl; stellar; Stl
Marker symbol: Sptssb
Marker name: serine palmitoyltransferase, small subunit B
Marker synonyms: 1110032A04Rik; ADMP; C3orf57; SSSPTB
Chromosome: 3
Strain of origin: A.B6-Tyr⁺/J
Molecular note: This ENU-induced A to T transversion of nucleotide 167 of the coding sequence results in a histidine to leucine change at amino acid 56, a highly conserved residue in vertebrates. This mutation increases the serine palmitoyltransferase (SPT) affinity toward the C18 fatty acyl-CoA substrate by twofold and elevates 20-carbon (C20) long chain base (LCB) production in the mutant mouse brain and eye.