B6.Cg-Tg(SMN2)11Tro Smn1^tm1Msd/J

Stock number: 008629
Strain synonyms: SMN2(N11);Smn+/-
Research areas: Neurobiology Research

Description

Mice that are homozygous for both the Smn1^tm1Msd allele and the Tg(SMN2)11Tro transgene (SMN2, survival of motor neuron 2, centromeric, human) exhibit a very severe phenotype with survival ranging from hours up to 7 days after birth. 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 allele and SMN2 (survival of motor neuron 2, centromeric, human) transgene, founder line 11, exhibit a very severe phenotype with survival ranging from hours up to 7 days after birth. Mice that die at or shortly after birth are slightly smaller than normal littermates. Mice that survive for several days are indistinguishable from normal littermates in the first 48 hours, after which they exhibit diminished weight gain. Mice hemizygous for the transgene and homozygous for the targeted mutation display 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 SMA-like 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 Tg(SMN2)11Tro transgenic mice 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)11Tro has been localized on chromosome 18. Mice hemizygous for the Tg(SMN2)11Tro transgene have 1 copy 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 11 were established and then mated to mice heterozygous for the Smn1^tm1Msd allele. The double mutant mice were then backcrossed to C57BL/6N 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 segregating.

Allele

Symbol: Tg(SMN2)11Tro
Name: transgene insertion 11, Thierry Bordet
MGI accession ID: MGI:3832059
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: SMN2(N11)
Marker symbol: Tg(SMN2)11Tro
Marker name: transgene insertion 11, Thierry Bordet
Marker synonyms: SMN2(N11)
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 11, which contains 1 copy 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.