FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(SMN2*A111G)591Ahmb/J

Stock number: 009134
Strain synonyms: FVB-Tg(SMN2*A111G)591Ahmb/J
Research areas: Neurobiology Research

Description

Mice that are homozygous for the Tg(SMN2*A111G)591Ahmb transgene (survival of motor neuron 2, centromeric, human), homozygous for the Smn1^tm1Msd (survival motor neuron 1) targeted mutation and hemizygous or homozygous for the Tg(SMN2)89Ahmb transgene are viable and survive for longer than one year. This mutant mouse strain may be useful in studies of spinal muscular atrophy.

Detailed description

Mice that are homozygous for the Tg(SMN2*A111G)591Ahmb transgene and homozygous for the Smn1^tm1Msd targeted mutation are not viable. Mice that are hemizygous for the Tg(SMN2*A111G)591Ahmb transgene, homozygous for the Smn1^tm1Msd targeted mutation and hemizygous or homozygous for the Tg(SMN2)89Ahmb transgene are viable and survive for longer than one year. The Jackson Laboratory has been unable to generate animals homozygous for all three alleles. Strong expression of the Tg(SMN2*A111G)591Ahmb transgene in founder line 591 is detected in the spinal cord, and weaker expression is detected in forebrain and liver by RT-PCR. This mutant mouse strain may be useful in studies of spinal muscular atrophy.

Importation of this model was supported by the Spinal Muscular Atrophy Foundation.

Development

A transgenic construct containing the SMN(A111G) missense mutation under the control of 4.1 kb SMN promoter was injected into fertilized FVB/N mouse eggs. Founder line 591 was subsequently established. Transgenic animals were bred to mice homozygous for the Tg(SMN2)89Ahmb transgene and heterozygous for the Smn1^tm1Msd targeted mutation (on a similar background to FVB.Cg-Tg(SMN2)89Ahmb Smn1^tm1Msd/J).

Allele

Symbol: Tg(SMN2*A111G)591Ahmb
Name: transgene insertion 591, Arthur H M Burghes
MGI accession ID: MGI:3847326
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(SMN2*A111G)591Ahmb
Marker name: transgene insertion 591, Arthur H M Burghes
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: SMN2,survival of motor neuron 2, centromeric,human
Molecular note: : A transgenic construct containing the SMN(A111G) missense mutation under the control of 4.1 kb SMN promoter was injected into fertilized FVB/N mouse eggs. Ten founder lines were obtained and line 588 was subsequently established. This line was found to have 5 copies of the transgene.

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.