B6;C3-Tg(SOD1*)D-14Dbo/J

Stock number: 027514
Product name: Cu-V103Z, SOD1, line D-14
Research areas: Neurobiology Research, Research Tools

Description

These Cu-V103Z, SOD1 line D-14 transgenic mice express a truncated human superoxide dismutase 1 incapable of copper binding and may be useful in studies of Amyotrophic Lateral Sclerosis (ALS).

Detailed description

Superoxide dismutase-1 is a soluble cytoplasmic antioxidant enzyme that contains copper and zinc. Mutations in the human SOD1 gene are a known cause of some familial amyotrophic lateral sclerosis cases. The Cu-V103Z transgenic construct that these mice carry contains a human SOD1 variant of genomic DNA (12 kb), in which the introns between exons 3, 4, and 5 have been removed. Mutations were introduced at histidines 46, 48, and 63, which eliminates copper binding, and a mutation that introduces a stop at the valine in position 103 to produce a truncated protein. Transgene expression is similar to expression levels observed in other transgenic models of motor neuron disease. Cu-V103Z (founder line D-14) develop paralysis between 16 and 24 months of age, but disease penetrance is incomplete. In transgenic mice exhibiting paralysis, SOD1 and ubiquitin immunoreactive fibrillar inclusions in spinal cord motor neurons. Mice hemizygous for the transgenic insert are viable and fertile. The Donating Investigator has not attempted to make the strain homozygous.

When crossed to a second transgenic line expressing wildtype human SOD1 (See Stock No. 002297), the resulting double transgenic mice exhibit an accelerated onset of paralysis with complete penetrance.

Development

The Cu-V103Z transgenic construct containing a truncated (at residue 103) human SOD1 variant with mutations at histidines 46, 48, and 63, and with the introns between exons 3, 4 and 5 removed, was injected into fertilized C3/B6 F2 mouse eggs. Founder line D-14 was subsequently established. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize B6C3F1/J oocytes (Stock No. 100010).

Allele

Symbol: Tg(SOD1*)D-14Dbo
Name: transgene insertion D-14, David R Borchelt
MGI accession ID: MGI:5621172
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SOD1*)D-14Dbo
Marker name: transgene insertion D-14, David R Borchelt
Chromosome: UN
Strain of origin: (C3H/HeJ x C57BL/6J)F2
Expressed genes: SOD1,superoxide dismutase 1,human
Site of expression: Widespread
Molecular note: This transgene contains a variant of human SOD1 that encodes a termination at codon position 103 (V103Z) with mutations at histidines at positions 46, 48, and 63 to R, Q, and G, respectively, to eliminate copper binding. In addition introns between exons 3, 4, and 5 of SOD1 were removed, creating a fragment with just two introns (one between exon 1 and 2 and one between exon 2 and 3) and exons 3, 4, and 5 fused to make one new exon. Two lines, E-17 and D-14, were established.