Phenotypes Associated with This Genotype

Genotype
MGI:7523309

• Allelic Composition: Stmn2^em1Jmi/Stmn2^em1Jmi
• Genetic Background: C57BL/6N-Stmn2^em1Jmi

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:337175 )

• although crosses of heterozygotes yield normal Mendelian ratios at E18.5, only 8% of homozygotes are obtained by 3 weeks of age

• however, very little premature death is observed after weaning

perinatal lethality, incomplete penetrance ( J:337175 )

• both sexes exhibit increased perinatal lethality

behavior/neurological

behavior/neurological phenotype ( J:337175 )

N • surviving homozygotes appear grossly normal with no obvious changes in mobility or paralysis up to 1 year of age

impaired coordination ( J:337175 )

• at 3 months of age, mice show a significant decrease in the length of time (s) before falling on an accelerating rotarod

decreased grip strength ( J:337175 )

• at 3 months of age, mice show a significant decrease in the latency time (s) to fall from an inverted screen, indicating impaired grip strength

increased mechanical nociceptive threshold ( J:337175 )

• at 3 months of age, mice show a significantly increased average 50% hindpaw withdrawal threshold in the Von Frey assay, indicating severely impaired mechanosensory perception

nervous system

nervous system phenotype ( J:337175 )

N • E18.5 embryos show normal diaphragm innervation with presynaptic terminals well apposed to postsynaptic AChR clusters and no significant changes in the numbers of primary and secondary neurites, length of primary branches, or number and size of AChR clusters relative to wild-type controls

N • at 3 months of age, conduction velocities are normal in both sensory and motor nerves, suggesting normal axon myelination

N • sciatic (mixed), femoral (primarily motor), and sural (primarily sensory) nerves show normal axon density at 3 and 12 months of age, suggesting lack of axon degeneration

N • no decrease in motor neuron number is noted in the lumbar spinal cord, suggesting lack of motor neuron death

abnormal neuron morphology ( J:337175 )

• mice develop early-onset sensory and motor neuropathy with behavioral deficits

delayed axon extension ( J:337175 )

• after 3 days in culture, axon outgrowth from embryonic DRG neurons is on average 35% shorter than that from wild-type neurons

abnormal motor neuron innervation pattern ( J:337175 )

• mice develop motor neuropathy with NMJ defects that preferentially affect distal, fast-fatigable motor units

abnormal neurite morphology ( J:337175 )

• E18.5 embryos show a mild but significant reduction in secondary neurite length in the phrenic nerve

abnormal axon morphology ( J:337175 )

• at 3 months of age, intraepidermal nerve fiber (IENF) density (number per millimeter of dermis) is significantly decreased in the footpad, suggesting a distal sensory neuropathy affecting small unmyelinated nerve fibers in the footpad skin

abnormal synaptic bouton morphology ( J:337175 )

• presynaptic terminals are rarely identified in lumbrical muscle NMJs; only remnants of an axon terminal are detected with an occasional Schwann cell present

• the few NMJs that remain intact display more circular mitochondria and synaptic vesicle depletion in the presynaptic terminal

abnormal neuromuscular synapse morphology ( J:337175 )

• distal lumbrical muscles -- mainly composed of fast-fatigable (FF) motor units -- show severely disorganized NMJs with little innervation of acetylcholine receptors (AChR) and marked endplate fragmentation; AChR clusters are fragmented with many small clusters that lack the typical pretzel morphology seen in wild-type clusters

• at 3 months of age, lumbrical NMJs show: (i) a complete absence of any presynaptic elements, (ii) occasional motor axons in the vicinity of some AChR clusters or (iii) apparently innervated endplate fragments with a severe presynaptic sprouting phenotype

• endplate fragmentation and presynaptic sprouting is consistent with presynaptic degeneration

• extensor digitorum longus (EDL), a fast-twitch muscle, shows marked NMJ denervation with >50% of all postsynaptic AChR clusters uninnervated; however, EDL pathology is less severe than the endplate fragmentation seen in distal lumbrical muscles

• no denervation is seen at NMJs of the slow-twitch soleus muscle

abnormal synaptic vesicle number ( J:337175 )

• the few NMJs that remain intact in distal lumbrical muscles show synaptic vesicle depletion in the presynaptic terminal

abnormal phrenic nerve morphology ( J:337175 )

• E18.5 embryos show a mild but significant reduction in secondary neurite length in the phrenic nerve

• however, peripheral nerve outgrowth and innervation of the diaphragm are grossly normal

abnormal action potential ( J:337175 )

• at 3 months of age, compound muscle action potential (CMAP) amplitude is significantly decreased after stimulation at the sciatic notch and recording at the foot

• however, the amplitude of sensory nerve action potential in the tail is normal, indicating minimal axon loss in sensory nerves

cellular

abnormal microtubule cytoskeleton morphology ( J:337175 )

• in vitro, kymographs of EB3-mNeonGreen movement showed that microtubules from E13.5 dorsal root ganglion (DRG) neurons exhibit a significant reduction in average frame velocity and total track displacement but normal track duration, indicating delayed microtubule polymerization

abnormal mitochondrial shape ( J:337175 )

• the few NMJs that remain intact in distal lumbrical muscles show more circular mitochondria in the presynaptic terminal

delayed axon extension ( J:337175 )

• after 3 days in culture, axon outgrowth from embryonic DRG neurons is on average 35% shorter than that from wild-type neurons

reproductive system

infertility ( J:337175 )

• mice do not breed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis		DOID:332	OMIM:PS105400	J:337175
neuropathy		DOID:870		J:337175