These SMN2; Smn; PrP92-SMN mutant mice harbor a targeted mutation and two trangenes, all independently created.
The Smn1tm1Msd targeted mutation was created in the laboratory of Dr. Michael Sendtner at the University of Wurzburg, Germany. Exon 2 of the targeted gene was disrupted with 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. Chimeric animals were crossed to C57BL/6 for an unspecified number of generations.
The PrP-SMN transgene was designed with the mouse prion protein gene (PrP or Prnp) promoter region and exon 1 and 2, full-length SMN cDNA (containing exons 1-8), and two SV40 polyA signals. This transgene was microinjected into fertilized FVB/N oocytes. Mice from founder line 92 (PrP92-SMN) were found to have 8-9 copies of the transgene.
The SMN2 transgene was created in the laboratory of Dr. Arthur Burghes at The Ohio State University. A 35.5 kb BamHI genomic fragment encoding the human SMN2 promoter and gene (derived from genomic clone PAC215P15) was injected into fertilized FVB/N mouse oocytes and founder animals obtained. Transgenic SMN2 mice from founder line 89 were established and found to contain one copy of the transgene (also called SMN2 low copy line 89).
These SMN2; Smn; PrP92-SMN mutant mice (heterozygous for the targeted mutation and homozygous for both transgenes) were maintained on a mixed genetic background (mostly FVB/N and C57BL/6) for many generations prior to arrival at The Jackson Laboratory.
