Table 2.

Available SMA mouse models for SMN2 splicing correction

Mouse Model	SMA I Monani et al. 2000 (5)	SMA I-III Hsieh-Li et al. 2000 (43)	SMAdelta7 Le et al. 2005 (3)	SMA I Michaud et al. 2010 (45)
Genetics	aSmn -/- cSMN2 bac +/+	bSmn -/- dSMN2 bac +/+	aSmn -/- cSMN2 bac +/+ SMN delta7 +/+	aSmn -/- eSMN2 +/-; fSMN2 +/-
Disease Onset	PND1	PND1	PND1-2	PND5
Survival	5.3-6 days	Type I: 10 days Type II: 2-4 weeks Type III: normal/ necrotic tail and hind limbs	13.3 days	15.2 days
Advantages	The carrier Smn +/- mice are long-lived and can be used for testing SMN2 splicing correction. Affected SMA mice are amenable to rescue of SMN protein levels and SMA phenotype.	The less severe mice are longer lived and have a mild phenotype of tail/hind limb necrosis. These mice can be used for testing SMN2 splicing and SMA phenotype correction.	Extension of lifespan over SMA I pups for ease in treatment of older pups. One can observe increases in SMN protein and rescue of the SMA phenotype.	Extension of lifespan over SMA I without the SMNdelta7 transgene. These mice can be used to evaluate SMN2 splicing and treatment of older pups
Disadvantages	The SMA affected mice have a very short lifespan and would require treatment when animals are neonates.	Variability in disease severity and short lifespan of SMA type I mice.	The SMNdelta7 transgene perturbs the observation of SMN2 splicing by RT-PCR. There are three loci to follow.	There are three loci to follow, and the SMN2 transgene loci need to be heterozygous to obtain the SMA mice.

^aSmn -/- allele due to exon 2 disruption by lacZ

^bSmn -/- allele due to exon 7 replacement with HPRT

^c28 kb human bac transgene with the SMN2 promoter and SMN2 gene (single copy of SMN2 at the transgene locus)

^d115 kb human bac transgene with SMN2, SERF1, and part of NAIP genes (two copies of SMN2 at the trangsgene locus)

^e35.5 kb human pac transgene with 1 copy of SMN2 at the transgene locus

^f35.5 kb human pac transgene with 2 copies of SMN2 at the transgene locus.