FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(S100B-EGFP)1Wjt Tg(SMN2*delta7)4299Ahmb/J

Stock number: 016573
Research areas: Neurobiology Research, Research Tools

Description

This s100 GFP SMA delta 7 mutant mouse strain may be useful in studies for visualization and vital imaging of neuromuscular junction Schwann cells in the etiology and pathology of Spinal Muscular Atrophy.

Detailed description

Mice that are homozygous for the targeted mutant Smn allele and homozygous for the Tg(SMN2*delta7)4299Ahmb and Tg(SMN2)89Ahmb transgenes exhibit symptoms and neuropathology similar to patients afflicted with proximal spinal muscular atrophy (SMA). At birth, triple mutants are noticeably smaller than normal littermates. By day 5, signs of muscle weakness are apparent and become progressively more pronounced over the following week as the mice display an abnormal gait, shakiness in the hind limbs and a tendency to fall over. Mean survival is approximately 13 days. Immunocytochemical analysis indicates that dystrophin expression is normal, however fibers isolated from the gastrocnemius muscle of a 14 day old triple mutant clearly show evidence of atrophy. These transgenic mice also express Enhanced Green Fluorescent Protein (EGFP) under the direction of the human S100 calcium-binding protein, beta (neural) promoter. Fluorescence is detected in Schwann cells at the neuromuscular junction. EGFP expression is detected at birth and fluorescence is also detected in Schwann cells of the sternomastoid, soleus, extensor digitorum longus, triangularis sterni and diaphragm muscles, some astrocytes, Bergmann glia and a few muscle macrophages. Presence of the Tg(S100B-EGFP)1Wjt transgene does not change the phenotype.

Development

This strain was generated by crossing Stock No. 005025 and Stock No. 005621 mice. The mice were then crossed to Stock No. 005025 mice for 11 generations.

Allele

Symbol: Tg(SMN2*delta7)4299Ahmb
Name: transgene insertion 4299, Arthur H M Burghes
MGI accession ID: MGI:3056918
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(SMN2*delta7)4299Ahmb
Marker name: transgene insertion 4299, Arthur H M Burghes
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: SMN2,survival of motor neuron 2, centromeric,human
Site of expression: Tg(SMN2*delta7)4299Ahmb
Molecular note: The transgene contains a human SMN2 promoter and a human SMN2 cDNA (SMNdelta7) that lacks exon 7. There are 14 copies of this allele integrated into the genome.

Allele

Symbol: Tg(S100B-EGFP)1Wjt
Name: transgene insertion 1, Wesley Thompson
MGI accession ID: MGI:3588512
Generation method: Transgenic
Attributes: Reporter
Marker symbol: Tg(S100B-EGFP)1Wjt
Marker name: transgene insertion 1, Wesley Thompson
Chromosome: UN
Strain of origin: (C57BL/6 x DBA/2)F2
Expressed genes: GFP,Green Fluorescent Protein,
Site of expression: Schwann cells of the sternomastoid, soleus, extensor digitorum longus, triangularis sterni and diaphragm muscles, some astrocytes, Bergmann glia and a few muscle macrophages. EGFP expression is detected at birth.
Molecular note: This transgene contains an Enhanced Green Fluorescent Protein gene under the control of the human S100 calcium-binding protein, beta (neural) promoter, which includes 6.6 kb of 5' flanking DNA, the first, noncoding exon and the first intron, including the 3' splice acceptor site. Fluorescence is detected in transgenic mice from birth in Schwann cells of the sternomastoid, soleus, extensor digitorum longus, triangularis sterni and diaphragm muscles, some astrocytes, Bergmann glia and a few muscle macrophages.

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.

Allele

Symbol: Grm7^{Tg(SMN2)89Ahmb}
Name: transgene insertion 89, Arthur H M Burghes
MGI accession ID: MGI:2448989
Generation method: Transgenic
Attributes: Hypomorph; Inserted expressed sequence; Humanized sequence
Marker symbol: Grm7
Marker name: glutamate receptor, metabotropic 7
Chromosome: 6
Strain of origin: FVB/N
Expressed genes: SMN2,survival of motor neuron 2, centromeric,human
Site of expression: Human SMN2 protein is expressed in the tissues examined (brain, liver, spinal cord) [Stock No. 005024].
Molecular note: A 35.5 kb genomic fragment containing the human survival motor neuron 2 (SMN2) gene and promoter was used for the transgene. The transgene is ubiquitously expressed in all tissues examined by Northern blot analysis. Line 89 carries 1 copy of the transgene integrated into intron 4 of the gene. RT-PCR confirmed reduced expression of the gene the transgene is integrated into.