129S1/SvImJ-Scn1a^em1Dsf/J

Stock number: 034129
Product name: SCN1A^R613X; Dravet model #10
Research areas: Neurobiology Research

Description

SCN1A^R613X mice carry an A to T point mutation in nucleotide 1837 (converting arginine (R) 613 to a STOP (X) codon) in addition to a silent C to T mutation at position 1833. The R613X nonsense mutation is expected to block the translation of complete protein from mRNA, enabling studies of readthrough therapeutics to restore protein function. On this 129S1/SvImJ genetic background, heterozygotes will likely demonstrate a mild (if any) Dravet Syndrome phenotype. Homozygotes are not viable.

Heterozygous progeny derived from a single cross with an inbred C57BL/6 mouse are anticipated to demonstrate significantly increased levels of spontaneous seizures, increased mortality by 4 weeks of age, cognitive impairment, hyperactivity, and motor abnormalities.

Of note, this strain is "open access", and available to for-profit organizations.

Detailed description

Dravet Syndrome is a rare form of epilepsy that begins in the first year of life. It is characterized by, among other things, frequent and/or prolonged seizures, behavioral and developmental delays, movement and balance issues, chronic infections, sensory integration disorders, and dysautonomia (disruptions of the autonomic nervous system that may affect body temperature regulation, heart rate, or blood pressure). Approximately 80% of Dravet Syndrome patients have a mutation in the SCN1A (sodium channel, voltage-gated, type I, alpha) gene.

SCN1A^R613X mice carry an A to T point mutation in nucleotide 1837 (converting arginine (R) 613 to a STOP (X) codon) in addition to a silent C to T mutation at position 1833. The R613X nonsense mutation, recurrent in Dravet Syndrome patients, is expected to block the translation of complete protein from mRNA, enabling studies of readthrough therapeutics to restore protein function. On this 129S1/SvImJ genetic background, heterozygotes will likely demonstrate a mild (if any) Dravet Syndrome phenotype. Homozygotes are not viable.

Heterozygous progeny derived from a single cross with an inbred C57BL/6 mouse (C57BL/6J (Stock 000664) or C57BL/6N) are anticipated to demonstrate significantly increased levels of spontaneous seizures, increased mortality by 4 weeks of age, cognitive impairment, hyperactivity, and motor abnormalities similar to those associated with a Scn1a knock-out allele (Stock No. 024761, lacking a nonsense mutation and readthrough capability).

Of note, this strain is "open access", and available to for-profit organizations.

Development

A CRISPR/Cas9-generated A>T point mutation at nucleotide 1837 (converting arginine (R) 613 to a STOP (X) codon) and a silent C>T mutation at position 1833 were introduced to exon 12 of the mouse Scn1a gene using 129S1/SvImJ embryos. Founder mice were bred with 129S1/SvImJ animals. N1 males, created by JAX Model Generation Services (JAX MGS) for the Dravet Syndrome Foundation (Spain), were transferred to the JAX Repository and maintained on a 129S1/SvImJ genetic background.

Allele

Symbol: Scn1a^em1Dsf
Name: endonuclease-mediated mutation 1, Dravet Syndrome Foundation
MGI accession ID: MGI:6342949
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: SCN1A^R613X
Marker symbol: Scn1a
Marker name: sodium channel, voltage-gated, type I, alpha
Marker synonyms: DEE6; DEE6A; DEE6B; DRVT; EIEE6; FEB3; FEB3A; FHM3; GEFSP2; HBSCI; NAC1; Nav1.1; SCN1; SMEI
Chromosome: 2
Strain of origin: 129S1/SvImJ
Molecular note: CRISPR/Cas9 genome editing is used to introduce an A>T point mutation at nucleotide 1837 (converting arginine (R) 613 to a STOP (X) codon) and a silent C>T mutation at position 1833 into exon 12. Mutations in Scn1a are associated with Dravet Syndrome.