FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2*A111G)588Ahmb Smn1^tm1Msd/J

Stock number: 008782
Research areas: Neurobiology Research

Description

Mice that are homozygous for the Tg(SMN2*A111G)588Ahmb 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.

Of note, for other mice carrying the same Tg(SMN2*A111G)588Ahmb transgene (Stock No. 031909), it was discovered that Tg(SMN2*A111G)588Ahmb integrated on chromosome 8 (119838039-119852117; mouse mm10]) and resulted in a 14 kb genomic region duplication that includes exons 1 and 2 of the Cotl1 locus. It is not known if the duplicated region expresses any Cotl1 isoforms or truncated protein.

Detailed description

Mice that are homozygous for the Tg(SMN2*A111G)588Ahmb transgene and homozygous for the Smn1^tm1Msd targeted mutation are not viable. Mice that are homozygous for the Tg(SMN2*A111G)588Ahmb 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. Expression of the Tg(SMN2*A111G)588Ahmb in founder line 588 is detected in the spinal cord, forebrain and liver by RT-PCR. This mutant mouse strain may be useful in studies of spinal muscular atrophy.

Tg(SMN2*A111G)588Ahmb transgene insertion information: For other mice carrying the same Tg(SMN2*A111G)588Ahmb transgene (Stock No. 031909), in October 2019, sequencing performed by The Jackson Laboratory discovered that three or more copies of the Tg(SMN2*A111G)588Ahmb transgene integrated on chromosome 8 (119838039-119852117; mouse mm10]) and resulted in a duplication of the 14 kb genomic region in between the two identified fusion points. This duplicated region includes exons 1 and 2 of the Cotl1 locus. It is not known if the duplicated region expresses any Cotl1 isoforms or truncated protein. Of note, endogenous Cotl1 has up to 5 exons, and exon 1 contains the ATG site in all 3 protein-coding transcripts [Ensembl GRCm38.p6].

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 588 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).

Tg(SMN2*A111G)588Ahmb transgene insertion information: For other mice carrying the same Tg(SMN2*A111G)588Ahmb transgene (Stock No. 031909), in October 2019, sequencing performed by The Jackson Laboratory discovered that three or more copies of the Tg(SMN2*A111G)588Ahmb transgene integrated on chromosome 8 (119838039-119852117; mouse mm10]) and resulted in a duplication of the 14 kb genomic region in between the two identified fusion points. This duplicated region includes exons 1 and 2 of the Cotl1 locus. It is not known if the duplicated region expresses any Cotl1 isoforms or truncated protein. Of note, endogenous Cotl1 has up to 5 exons, and exon 1 contains the ATG site in all 3 protein-coding transcripts [Ensembl GRCm38.p6].

Allele

Symbol: Tg(SMN2*A111G)588Ahmb
Name: transgene insertion 588, Arthur H M Burghes
MGI accession ID: MGI:3847324
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(SMN2*A111G)588Ahmb
Marker name: transgene insertion 588, Arthur H M Burghes
Chromosome: 8
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. Eleven founder lines were obtained and line 588 was subsequently established. This line was found to have 4 copies of the transgene. The transgene integrated on chromosome 8 (119838039-119852117; mouse mm10]), which resulted in a duplication of the 14 kb genomic region in between the two identified fusion points. This duplicated region includes exons 1 and 2 of the Cotl1 locus. It is not known if the duplicated region expresses any Cotl1 isoforms or truncated protein.

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.