Phenotypes associated with this allele

• Allele Symbol: Musk^tm2Vwi
• Allele Name: targeted mutation 2, Veit Witzemann
• Allele ID: MGI:3815474
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Musk^tm2Vwi/Musk^tm2Vwi	Not Specified	MGI:3815536
ht2	Musk^tm1.1Vwi/Musk^tm2Vwi	Not Specified	MGI:3815537

Genotype
MGI:3815536

hm1

• Allelic Composition: Musk^tm2Vwi/Musk^tm2Vwi
• Genetic Background: Not Specified

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

mortality/aging

mortality/aging ( J:141024 )

N • mice exhibit a normal lifespan

muscle

muscle phenotype ( J:141024 )

N • mice show no signs of muscle weakness

behavior/neurological

behavior/neurological phenotype ( J:141024 )

N • mice exhibit normal behavior

growth/size/body

growth/size/body region phenotype ( J:141024 )

N • mice are of normal weight

Genotype
MGI:3815537

ht2

• Allelic Composition: Musk^tm1.1Vwi/Musk^tm2Vwi
• Genetic Background: Not Specified

mortality/aging

premature death ( J:141024 )

• 40% of male mice die between the second and fourth month of life

• however, female mice do not exhibit premature death

muscle

thin diaphragm muscle ( J:141024 )

decreased skeletal muscle mass ( J:141024 )

• after 3 weeks, mice exhibit reduced muscle mass compared to wild type mice in the pelvic and scapular regions

abnormal muscle electrophysiology ( J:141024 )

• muscle strength produced by single or titanic stimuli is reduced compared to in wild-type mice while the degree of fatigue remains the same

• the time to peak or contraction time and half relaxation time of a direct-evoked single twitch is prolonged compared to in wild-type muscle

• unlike in wild-type mice, the diaphragm is unable to maintain unique tentanic contractions or repetitive titanic contractions indicating reduced fatigue resistance

• the twitch to titanic ratio of the diaphragm after nerve stimulation is double wild-type

muscle weakness ( J:141024 )

• mice exhibit weakness of the pelvic muscle that leads to a waddling gait unlike

nervous system

abnormal axon extension ( J:141024 )

• axons of the nerves innervating the diaphragm exhibit overgrowth and increased branching compared to in wild-type mice

abnormal innervation ( J:141024 )

• axons are increased in length and extend from the main nerve trunk to the medial and/or lateral side of the diaphragm compared to in wild-type mice

abnormal neuromuscular synapse morphology ( J:141024 )

• unlike in wild-type mice, axons at the NMJs in the diaphragm exhibit sprouting and retraction bulbs and fail to form the normal Pretzel-like shaped post-synpatic structure

• as early as P0, endplates in the diaphragm NMJs are smaller and more spread out than in wild-type mice

• at P25 and P45, diaphragm neuromuscular junctions (NMJs) lack a well-defined central endplate unlike in wild-type mice

• at P45, the NMJs of the intercostals, diaphragm and tibialis anterior exhibit altered post-synaptic structures compared to in wild-type mice

• at P120, soleus NMJs exhibit few junctional folds, the distance between the post-synaptic membrane and myofibril compartment is reduced compared to in wild-type mice, mitochondria invade the subsynpatic space, subsynaptic nuclei disappear, and in many cases the sole plate is abolished

• however, extensor digitorum longus NMJs are normal

abnormal endplate potential ( J:141024 )

• the amplitude of endplate potentials is 76% of wild-type

abnormal miniature endplate potential ( J:141024 )

• the mean peak frequency of miniature end plate potential of the diaphragm is reduced compared to in wild-type diaphragms

• however, the amplitudes of miniature end plate potentials is normal

behavior/neurological

impaired coordination ( J:141024 )

• in a rotarod test, the latency to fall is half of wild-type

decreased grip strength ( J:141024 )

• mice exhibit a progressive loss of grip strength beginning at P21 and reaching a 30% reduction by P60 compared to wild-type mice

abnormal gait ( J:141024 )

• mice develop a waddling gait

skeleton

abnormal spine curvature ( J:141024 )

• after 3 weeks, mice exhibit deformation of the backbone and increasing kyphosis unlike in wild-type mice

• at P45, mice exhibit curvatures of the spine in the thoracic and lumbar vertebrae

kyphosis ( J:141024 )

growth/size/body

decreased body weight ( J:141024 )

• by 2 months of age mice weigh 75% of wild-type

cellular

abnormal axon extension ( J:141024 )

• axons of the nerves innervating the diaphragm exhibit overgrowth and increased branching compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myasthenic syndrome 9		DOID:0110670	OMIM:616325	J:141024