B6.Cg-Tg(SMN2)11Tro Tg(SMN2)46Tro Smn1^tm1Msd/J

Stock number: 008631
Strain synonyms: SMN2(N11, N46);Smn+/-
Research areas: Neurobiology Research

Description

Triple mutant mice that are homozygous for the Smn1^tm1Msd allele and hemizygous for the two transgenes, Tg(SMN2)11Tro and Tg(SMN2)46Tro, exhibit diminished weight gain, progressive muscle weakness, necrotic lesions and loss of neurons in the sciatic nerve. This mutant mouse strain may be useful in neuromuscular studies related to Spinal Muscular Atrophy (SMA).

Detailed description

Mice that are homozygous for the Smn1^tm1Msd allele and hemizygous for the two transgenes, Tg(SMN2)11Tro and Tg(SMN2)46Tro, exhibit symptoms and neuropathology similar to patients afflicted with severe proximal spinal muscular atrophy (SMA). Triple mutants are indistinguishable from normal littermates in the first 4 days, after which they exhibit diminished weight gain. By 7 days of age, signs of muscle weakness are apparent and become progressively more pronounced over the following week as the mice display an abnormal gait. Mean survival is approximately 15 days although a few animals (<3%) can survive longer. Histological analysis indicates that 15 day old mice have a reduced number of lumbar motor neurons and axons in sciatic nerve. Gastrocnemius muscles at the same age clearly show evidence of atrophy. Triple mutant mice develop progressive and severe necrotic lesions of the tail, ears and teeth. Mice hemizygous for both transgenes and heterozygous for the targeted mutation do not exhibit SMA-like phenotype. This mutant mouse strain may be useful in neuromuscular studies related to Spinal Muscular Atrophy (SMA).

Development

These triple mutant mice were created by crossing females from Stock No. 008630 and males from Stock No. 008629. The two randomly inserted transgenes segregate independently.

Allele

Symbol: Tg(SMN2)46Tro
Name: transgene insertion 46, Thierry Bordet
MGI accession ID: MGI:3832058
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SMN2)46Tro
Marker name: transgene insertion 46, Thierry Bordet
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: SMN2,survival of motor neuron 2, centromeric,human
Molecular note: A 35.5 kb Ba mHI genomic fragment encoding the human SMN2 promoter and gene (derived from genomic clone PAC215P15) was injected into fertilized FVB/N mouse oocytes. Transgenic SMN2 mice from founder line 46, which contains 2 copies of the transgene, were established.

Allele

Symbol: Tg(SMN2)11Tro
Name: transgene insertion 11, Thierry Bordet
MGI accession ID: MGI:3832059
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SMN2)11Tro
Marker name: transgene insertion 11, Thierry Bordet
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: SMN2,survival of motor neuron 2, centromeric,human
Molecular note: A 35.5 kb Ba mHI genomic fragment encoding the human SMN2 promoter and gene (derived from genomic clone PAC215P15) was injected into fertilized FVB/N mouse oocytes. Transgenic SMN2 mice from founder line 11, which contains 1 copy of the transgene, were established.

Allele

Symbol: Smn1^tm1Msd
Name: targeted mutation 1, Michael Sendtner
MGI accession ID: MGI:2183946
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Smn1
Marker name: survival motor neuron 1
Chromosome: 13
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: The expression of the lacZ gene in tissues where Smn is normally expressed was noted.
Molecular note: A lacZ-neo cassette was inserted into exon 2 by homologous recombination resulting in an in-frame fusion of lacZ to exon 2. Homozygous mutant embryos were identified up to 80 hours post coitum. The expression of the lacZ gene in tissues where Smn is normally expressed was noted.