cardiovascular system phenotype

• decreased heart rate
  • 9 month old mutants exhibit lower average heart rate than controls
  (MGI Ref ID J:186987)
  • Normal - however, mutants do not exhibit a longer PR or QRS interval, indicating that mutants do not exhibit bradyarrhythmia
  (MGI Ref ID J:186987)

• abnormal blood vessel morphology
  • thermal imaging indicates that vascular destruction in the tail occurs before overt exterior necrosis
  (MGI Ref ID J:186987)
  • lateral vasculature of the tail is primarily affected, with a loss of integrity in the vessel wall (most evident in the inner tunica intima of the small lateral vasculature) whereas the ventral artery remains intact until the very last stages of necrosis
  (MGI Ref ID J:186987)

cellular phenotype

• tail necrosis
  • tail necrosis at 20-40 days of age is characterized by disorganization of muscle fiber bundles along with loss of intact vasculature in the absence of an inflammatory lesion as mice age
  (MGI Ref ID J:186987)
  • onset of tail necrosis is seen as early as P5 and progresses to complete loss of the tail by 45 days of age
  (MGI Ref ID J:186987)

• epidermal necrosis
  • mutants present with progressive necrosis of peripheral body parts beginning with the tail and moving toward the hindlimbs and then to the pinnae of the ears
  (MGI Ref ID J:186987)

growth/size/body region phenotype

• decreased body size
  • by P15 and P20, males and females, respectively, are smaller than wild-type controls
  (MGI Ref ID J:186987)

integument phenotype

• epidermal necrosis
  • mutants present with progressive necrosis of peripheral body parts beginning with the tail and moving toward the hindlimbs and then to the pinnae of the ears
  (MGI Ref ID J:186987)

• hyperalgesia
  (MGI Ref ID J:186987)

• decreased thermal nociceptive threshold
  • ous stimulus of 52C is seen
  (MGI Ref ID J:186987)
  • 6-8 week old mutants exhibit robust sensitization in the evaporative cooling assay, responding more vigorously than controls, indicating increased sensitivity to temperature
  (MGI Ref ID J:186987)
  • 6-8 week old mutants (with no paw necrosis) exhibit an increase in sensitivity to moderately noxious heat with a significant decrease in hindpaw withdrawal latencies when placed on a 45C and 48C metal plate, however no differences in response to high noxious stimulus of 52C is seen
  (MGI Ref ID J:186987)

• hyperresponsive to tactile stimuli
  • in plantar von Frey testing, 6-8, 20 and 24 week old mutants show significantly lower paw withdrawal force than controls, indicating hyperalgesia
  (MGI Ref ID J:186987)

limbs/digits/tail phenotype

• tail necrosis
  • onset of tail necrosis is seen as early as P5 and progresses to complete loss of the tail by 45 days of age
  (MGI Ref ID J:186987)
  • tail necrosis at 20-40 days of age is characterized by disorganization of muscle fiber bundles along with loss of intact vasculature in the absence of an inflammatory lesion as mice age
  (MGI Ref ID J:186987)

muscle phenotype

• decreased skeletal muscle fiber size
  (MGI Ref ID J:186987)

nervous system phenotype

• abnormal endplate potential
  • at P350, 15% of junctions in splenius muscles are silent in the functional junctions that remain
  (MGI Ref ID J:186987)
  • at P90, about 8% of junctions in splenius muscle are silent, where MEPPs could be recorded, but nerve stimulation did not elicit endplate potentials (EPPs)
  (MGI Ref ID J:186987)

• abnormal neuromuscular synapse morphology
  • Normal - however, at P8 and P14, all NJMs are innervated and no nerve sprouting is seen, indicating that synapse formation at the NJM is not affected in mutants
  (MGI Ref ID J:186987)
  • rminals, and nerve terminal sprouting, indicating that synaptic maintenance is mildly disrupted
  (MGI Ref ID J:186987)
  • at P90, about 10% of neuromuscular junctions (NMJs) in splenius, longissimus, and semispinalis muscles show abnormal morphology, with fragmented acetylcholine receptor clusters, abnormal thin nerve terminals, some junctions innervated by multiple nerve terminals, and nerve terminal sprouting, indicating that synaptic maintenance is mildly disrupted
  (MGI Ref ID J:186987)

• abnormal synaptic transmission
  • reduction in synaptic transmission efficacy in muscle
  (MGI Ref ID J:186987)
  • Normal - however, mutants exhibit normal number of motor axons in the lumbar 3 and lumbar 4 ventral roots at P350 and no significant loss of VGLUT1-positive synapses in L1-2 motoneurons
  (MGI Ref ID J:186987)

• abnormal miniature endplate potential
  • at P90 and P350, muscle exhibits a slight increase in the spontaneous miniature endplate potential (MEPP) amplitude
  (MGI Ref ID J:186987)
  • Normal - however, no difference from controls is seen in the MEPP frequency or the evoked endplate potential (EPP) amplitudes
  (MGI Ref ID J:186987)
  • upon nerve stimulation, the quantal content is decreased by 13-14% in both mutants at P90 and P350
  (MGI Ref ID J:186987)

behavior/neurological phenotype

• enhanced coordination
  • mutants perform better than controls on the accelerated rotarod test and marginally better on the constant speed rotarod test at 1 month of age
  (MGI Ref ID J:186987)
  • Normal - however, forelimb grip strength is normal at 24 and 52 weeks of age
  (MGI Ref ID J:186987)

• decreased thermal nociceptive threshold
  • 6-8 week old mutants (with no paw necrosis) exhibit an increase in sensitivity to moderately noxious heat with a significant decrease in hindpaw withdrawal latencies when placed on a 45C and 48C metal plate, however no differences in response to high noxious stimulus of 52C is seen
  (MGI Ref ID J:186987)
  • ous stimulus of 52C is seen
  (MGI Ref ID J:186987)
  • 6-8 week old mutants exhibit robust sensitization in the evaporative cooling assay, responding more vigorously than controls, indicating increased sensitivity to temperature
  (MGI Ref ID J:186987)

• hyperalgesia
  (MGI Ref ID J:186987)

• hyperresponsive to tactile stimuli
  • in plantar von Frey testing, 6-8, 20 and 24 week old mutants show significantly lower paw withdrawal force than controls, indicating hyperalgesia
  (MGI Ref ID J:186987)

mammalian phenotype

• no phenotypic analysis
  • Normal - no phenotypic analysis available
  (MGI Ref ID J:135425)

skeleton phenotype

• decreased bone mineral density
  • 6 month old mutants exhibit lower bone mineral density
  (MGI Ref ID J:186987)

• decreased bone mineral content
  • 6 month old mutants exhibit lower bone mineral content
  (MGI Ref ID J:186987)

skeleton phenotype

• decreased bone mineral content
  • 6 month old mutants exhibit lower bone mineral content
  (MGI Ref ID J:186987)

• decreased bone mineral density
  • 6 month old mutants exhibit lower bone mineral density
  (MGI Ref ID J:186987)