These double mutant mice were generated by crossing transgenic mice, founder line 46, with Smn1tm1Msd 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 Smn1tm1Msd 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.
