FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd/2J

Stock number: 007949
Product name: FVB.SMN2;Smn- , Severe Type I SMA , Burghes' Severe Model FVB/NJ congenic
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Mice that are homozygous for the Tg(SMN2)89 transgene and the Smn1 null mutation exhibit symptoms and neuropathology similar to patients with severe type I proximal spinal muscular atrophy (SMA). Homozygous mice fully congenic on the FVB/NJ genetic background (N10; Stock No. 007949) may exhibit phenotype differences compared to the incipient congenic FVB/N homozygous colony (N5; Stock No. 005024).

Detailed description

FVB/N-congenic mice homozygous for the Tg(SMN2)89 transgene (SMN2+/+) and homozygous for the Smn1^tm1Msd mutation (Smn-/-) are a severe type I SMA mouse model. Homozygous mice fully congenic on the FVB/N genetic background (N10; Stock No. 007949) may exhibit phenotype differences compared to the incipient congenic FVB/N homozygous colony (N5; Stock No. 005024). The phenotype differences between these two strains, if any, have not yet been completely characterized (June 2013). Also note, Stock No. 005024 does not survive as hemizygous for the Tg(SMN2)89 transgene (SMN2+/-) and homozygous for the Smn1^tm1Msd mutation (Smn-/-).

Development

These B6.SMN2;Smn- mice harbor the Tg(SMN2)89 transgene and the Smn1 null allele (Smn1^tm1Msd). The creation of the transgene and targeted mutation are described for the severe type I SMA mouse model on an incipient FVB/N congenic background; Stock No. 005024. Note the Tg(SMN2)89 transgene insertion site in on chromosome 6. FVB.SMN2;Smn- mice that had been backcrossed onto FVB/N for five generations (N5; Stock No. 005024) were obtained and then backcrossed onto FVB/NJ for additional generations. The strain after ten generations of backcrossing is FVB/NJ fully congenic FVB.SMN2;Smn- (N10; Stock No. 007949).

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.