Phenotypes Associated with This Genotype

Genotype
MGI:5490787

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1-SMN2*)16Cll/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:194969 )

• mean lifespan is 34 days, with mutants living longer than double homozygous Smn1^tm1Msd and Tg(SMN2)89Ahmb control mice

• nearly 25% of mutants live beyond 40 days, with several living beyond P70

growth/size/body

decreased body size ( J:194969 )

• smaller size compared to wild-type controls at P12, although weight is greater than in double homozygous Smn1^tm1Msd and Tg(SMN2)89Ahmb control mice and some mutants eventually reach the weight of unaffected mice

behavior/neurological

behavior/neurological phenotype ( J:194969 )

N • mutants are more agile and generally fitter than double homozygous Smn1^tm1Msd and Tg(SMN2)89Ahmb control mice

impaired righting response ( J:194969 )

• 20-70% of mutants at P5-15 are able to right themselves compared to 100% of unaffected control mice (mice homozygous for Tg(SMN2)89Ahmb and heterozygous for Smn1^tm1Msd)

• starting at P5, mutants show increased ability to right compared to triple transgenics homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb (20-70% vs. 3-15% in the controls)

impaired coordination ( J:194969 )

• mutants stay on the rotorod for shorter periods of time than unaffected controls (mice homozygous for Tg(SMN2)89Ahmb and heterozygous for Smn1^tm1Msd)

decreased grip strength ( J:194969 )

• mutants show a slight decrease in grip strength compared to unaffected controls (mice homozygous for Tg(SMN2)89Ahmb and heterozygous for Smn1^tm1Msd)

muscle

decreased skeletal muscle fiber size ( J:194969 )

• skeletal muscle fibers are smaller than in wild-type controls, however they are larger than in triple transgenics homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

nervous system

abnormal neuromuscular synapse morphology ( J:194969 )

• mutants show an approximate 60% reduction of proprioceptive synapses onto motor neurons compared to triple transgenics homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

• P19 mutants show an increase in the percentage of neuromuscular junctions with perforated or fragmented endplates compared to controls homozygous for Tg(SMN2)89Ahmb, indicating a defect in synapse maturation

• mutants exhibit a modest but significant reduction in neuromuscular junction innervation in the longissimus muscle

cardiovascular system

thin interventricular septum ( J:194969 )

• mutants show a slight reduction in interventricular septum thickness, although this does not reach significance

• the interventricular septum thickness is significantly improved compared to triple transgenic controls homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

cardiac interstitial fibrosis ( J:194969 )

• mutants exhibit a modest, but significant increase in cardiac interstitial fibrosis compared to unaffected wild-type controls

• interstitial fibrosis is significantly improved when compared to triple transgenic controls homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

integument

epidermal necrosis ( J:194969 )

• mutants start to show signs of necrosis on the ears, tails, and/or eyes at approximately P40-P50

cellular

cardiac interstitial fibrosis ( J:194969 )

• mutants exhibit a modest, but significant increase in cardiac interstitial fibrosis compared to unaffected wild-type controls

• interstitial fibrosis is significantly improved when compared to triple transgenic controls homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:194969