Phenotypes Associated with This Genotype

Genotype
MGI:3663312

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

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

mortality/aging

premature death ( J:81238 )

• mean survival is 227 days

nervous system

abnormal motor neuron morphology ( J:81238 )

decreased motor neuron number ( J:81238 )

• 29% fewer lumbar spinal cord neurons than control in 3.5 month old mice

• 19% fewer facial nucleus neurons than control

• 5 day old mice did not exhibit reduced numbers of motor neurons

motor neuron degeneration ( J:81238 )

abnormal axon morphology ( J:81238 )

• ventral roots from L1-L5 lumbar spinal cord region contain few myelinated axons

• remaining axons are shriveled and exhibit Wallerian degeneration

abnormal neuromuscular synapse morphology ( J:81238 )

• increased number of neuromuscular junctions in gastrocnemius

neuronal intranuclear inclusions ( J:81238 )

• intranuclear aggregates (gems) of the SMN protein in spinal cord are fewer and less intense than in normal littermates

abnormal action potential ( J:81238 )

• reduced amplitudes in evoked muscle potentials from tibial nerve

abnormal motor nerve collateral sprouting ( J:81238 )

• axon sprouting occurs in gastrocnemius and triceps muscles

• sprouts are both nodal and emerge from the neuromuscular junction (terminal)

muscle

muscular atrophy ( J:81238 )

• angulated and atrophic fibers observed in gastrocnemius and to a lesser extent in quadriceps and intercostal muscles

abnormal muscle electrophysiology ( J:81238 )

• samples from multiple pelvic and thoracic muscles exhibit abnormal spontaneous activity of single muscle fibers and of motor units in 4-6 month old mice

• abnormal activity is occasionally accompanied by biphasic sharp waves

growth/size/body

decreased body size ( J:81238 )

• 20-40% smaller than normal littermates

weight loss ( J:81238 )

• toward the end of life

reproductive system

reduced fertility ( J:81238 )

behavior/neurological

poor grooming ( J:81238 )

• mice fail to groom efficiently toward the end of life

limb grasping ( J:81238 )

• muscle weakness exhibited by 3 weeks of age

decreased locomotor activity ( J:81238 )

• mice are less active by 3 weeks of age compared to normal littermates

• exhibit very little activity toward the end of life

respiratory system

hypopnea ( J:81238 )

• mice exhibit short, shallow breeding toward the end of life

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile spinal muscular atrophy		DOID:12376	OMIM:253400	J:81238