Figure 1.

Diagram of Floxed Smn alleles and crosses used in this study. (A) The disrupted Smn allele is referred to as Smn^KO (37). The Floxed exon 7 Smn allele is referred to as Smn^F7 before recombination (32). After recombination when exon 7 is deleted the allele is called Smn^D7. For the replacement of Smn, the allele termed Smn^INV, contains human Smn exon 7 with flanking regions of intron followed by an inverted copy of mouse Smn exon 7 with flanking regions of intron (24,38). The two copies of exon 7 were cloned in between lox66 and a lox71 sites. Upon activation of recombination by a Cre driver the area between the lox sites is inverted resulting in a functional Smn exon 7 followed by an inverted SMN exon 7. After recombination this allele is referred to as Smn^Re. In all crosses the Smn^INV or Smn^F7 alleles were crossed to mice that were heterozygous for the Smn^KO allele and contained a Cre driver. Thus all affected animals reported here are Smn^D7/KO or Smn^Re/KO after recombination. (B) Mice containing a Cre driver and heterozygous for the Smn knockout allele (Smn^KO) were crossed to mice homozygous for the floxed exon7 Smn^F7 allele. Upon recombination the floxed exon7 Smn allele is referred to as Smn^D7. Similarly, mice that contain a Cre driver and are heterozygous for the Smn knockout allele (Smn^KO) were crossed to mice heterozygous for the floxed exon7 Smn^INV allele. Mice homozygous for the Smn^INV allele are not viable beyond 21 days of age. Upon recombination the floxed exon7 Smn allele is referred to as Smn^Re. Note that the progeny of these crosses only contain one deletion or replacement Smn allele over the Smn^KO knockout allele. This is to ensure maximal efficiency of the Cre driver on just one target allele. Moreover, the progeny of these crosses were only used for data analysis and not for breeding to eliminate the possibility of germ line recombination.