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

Stock number: 008630
Strain synonyms: SMN2(N46);Smn+/-
Research areas: Neurobiology Research

Description

Mice that are homozygous for the Smn1^tm1Msd allele and the Tg(SMN2)46Tro (SMN2, survival of motor neuron 2, centromeric, human) transgene do not display a SMA-like phenotype. Necrotic lesions are observed on the tail, ears and teeth. This mutant mouse strain may be useful in neuromuscular studies involving Spinal Muscular Atrophy (SMA).

Detailed description

Mice that are homozygous for both the Smn1^tm1Msd targeted mutation and the SMN2, survival of motor neuron 2, centromeric, human, transgene (founder line 46) are viable, fertile and do not display a SMA-like phenotype. Necrotic lesions are observed on the tail, ears and teeth. Mice that are hemizygous for the transgene and homozygous for the targeted mutation have an embryonic lethal phenotype. Mice that are heterozygous for the Smn1^tm1Msd allele and homozygous for the SMN2 transgene are viable, fertile and do not exhibit neuropathy. Mice homozygous for the transgene (and wildtype at the Smn1 locus) do not exhibit an abnormal phenotype. This mutant mouse strain may be useful in neuromuscular studies involving Spinal Muscular Atrophy (SMA).

Development

These double mutant mice were generated by crossing transgenic mice, founder line 46, with Smn1^tm1Msd targeted mutant mice.
The targeted mutant allele was created in the laboratory of Dr. Michael Sendtner at the University of Wurzburg, Germany. Exon 2 of the endogenous mouse Smn gene was disrupted by employing a targeting vector encoding a neomycin cassette and a lacZ gene fused to the first 40 nucleotides of the disrupted exon to permit expression of the lacZ gene in tissues where Smn is normally expressed. The construct was electroporated into 129P2/OlaHsd-derived E14Tg2a-IV embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals obtained. Chimeric animals were crossed to C57BL/6 for an unspecified number of generations. The Donating Investigator reports that the Tg(SMN2)46Tro has been localized on chromosome 3. Mice hemizygous for the transgene have 2 copies of the transgene.
The SMN2 transgene was created at Trophos (Marseilles, France). 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 were established and then mated to mice heterozygous for the Smn1^tm1Msd allele. The donating investigator reported that the double mutant mice were then backcrossed to C57BL/6N (see SNP note below) for at least 15 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6J. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6 genetic background.

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
Synonyms: SMN2(N46)
Marker symbol: Tg(SMN2)46Tro
Marker name: transgene insertion 46, Thierry Bordet
Marker synonyms: SMN2(N46)
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: Smn1^tm1Msd
Name: targeted mutation 1, Michael Sendtner
MGI accession ID: MGI:2183946
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: SMN^-
Marker symbol: Smn1
Marker name: survival motor neuron 1
Marker synonyms: BCD541; C-BCD541; GEMIN1; SMA; SMA@; SMA1; SMA2; SMA3; SMA4; Smn; SMNC; SMNT; T-BCD541; TDRD16A; TDRD16B
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.