Phenotypes Associated with This Genotype

Genotype
MGI:3785610

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb
• Genetic Background: FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb/J

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

mortality/aging

postnatal lethality, complete penetrance ( J:164446 )

• average survival of about 2 weeks

nervous system

abnormal sympathetic system morphology ( J:164446 )

• TH staining of the heart to visualize sympathetic innervation indicates that mutants exhibit fewer major neuronal branches and they appear thinner and less distinct

abnormal innervation pattern to muscle ( J:132467 )

• mice preferentially lack innervation of the caudal band of the levator auris longus

abnormal neuromuscular synapse morphology ( J:132467 )

• many endplates are partially occupied or vacant unlike in wild-type mice

• mice exhibit both post- and pre-synaptic pathology at motor neuron endplates

muscle

dilated cardiomyopathy ( J:164446 )

decreased skeletal muscle fiber diameter ( J:132467 )

• muscle fiber diameter is decreased in both slow- and fast-twitch muscles compared to in wild-type mice

cardiovascular system

abnormal heart morphology ( J:164446 )

• hearts appear flaccid and lack defined shape and gross attenuation of walls at P10 and P13

dilated cardiomyopathy ( J:164446 )

abnormal blood flow velocity ( J:164446 )

• echocardiography indicates that P6 mice exhibit deficiencies in blood flow out of the right ventricle at the pulmonary valve, with decreased peak velocity and peak gradient, indicating a reduction in pumping efficiency and blood flow from the right ventricle to the lungs

increased heart rate variability ( J:164446 )

• as mice near end of life, they display a large increase in heart rate variability, ultimately displaying adjacent RR intervals that are highly inconsistent

decreased heart rate ( J:164446 )

• mice present bradycardia as early as 2 days of age, before neuromuscular symptoms

• bradyarrhythmia is characterized by progressive heart block and reduced ventricular depolarization efficiency

prolonged PR interval ( J:164446 )

• at P4, mice have a first-degree heart block characterized by elongated PR interval durations

• at P10, sharp increase in the PR interval and breakdown of cardiac rhythm as mutants exhibit progressive heart block

prolonged QRS complex duration ( J:164446 )

• elongation of the time of ventricular depolarization through an increase in QRS interval duration beginning at P4

growth/size/body

decreased body size ( J:164446 )

weight loss ( J:164446 )

• begin to lose weight at around P10

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:164446