nervous system phenotype

• demyelination
  • in the sciatic nerve at P12
  (MGI Ref ID J:158973)

mortality/aging

• postnatal lethality, incomplete penetrance
  • homozygotes with severe forelimb abnormalities often die within 2 to 3 days after birth due to difficulties in positioning themselves for suckling and thus do not get enough nourishment, however if they do survive the first few weeks, their condition usually begins to improve and some have a relatively normal lifespanlly begins to improve and some have a relatively normal lifespan
  (MGI Ref ID J:11392)

growth/size/body region phenotype

• decreased body size
  • adults with forelimb abnormalities are almost always smaller than controls
  (MGI Ref ID J:11392)

nervous system phenotype

• abnormal axon morphology
  • the axons that are enclosed by promyelin fibers have smaller axon calibers than those of myelinated fibers
  (MGI Ref ID J:11392)

• abnormal myelin sheath morphology
  • in some mutants, the ratio of myelin sheath thickness to axon caliber is reduced
  (MGI Ref ID J:24743)
  • variable degree of generalized hypomyelination, with peripheral myelin sheaths thinner relative to axonal size than in controls
  (MGI Ref ID J:11392)

• abnormal myelination
  • all homozygotes have delayed and abnormal myelination of the peripheral nervous system but not the central nervous system
  (MGI Ref ID J:11392)
  • delay in myelination and a persistence of some axons and Schwann cells in the promyelin configuration throughout life
  (MGI Ref ID J:24743)
  • failure of myelination in some fibers leads to persistent promyelin fibers with small axons, especially in muscles that normally have small axons
  (MGI Ref ID J:11392)
  • neuron-Schwann cell cocultures from E13 dissociated dorsal root ganglia do not myelinate
  (MGI Ref ID J:105260)

• abnormal nervous system morphology
  • all peripheral nerves are hypotrophic
  (MGI Ref ID J:105260)
  • exhibit a variable increase in peripheral nerve fasciculation and an occasional mild increase in endoneural connective tissue, however no differences in the number of Schwann cells or any evidence of denervation atrophy
  (MGI Ref ID J:11392)

• abnormal sciatic nerve morphology
  • hypertrophy of the sciatic nerve
  (MGI Ref ID J:105260)

limbs/digits/tail phenotype

• abnormal digit morphology
  • fingers are flexed
  (MGI Ref ID J:24743)

• abnormal forelimb morphology
  • flexed forelimbs (fingers, wrists, shoulders), elbows rotated inwards
  (MGI Ref ID J:24743)
  • forelimbs with abnormal postures are held flexed at one or more of the shoulder, wrist or digital joints but extended at the elbow, resulting in the forelimbs being pointed toward the hindlimbs
  (MGI Ref ID J:11392)

• abnormal hindlimb morphology
  • hindlimbs are more subtly affected than forelimbs, with the most common abnormality a mild, usually symmetrical, weakness of hindpaw dorsiflexion
  (MGI Ref ID J:11392)

• abnormal limb morphology
  • abnormally flexed joints can be extended early in life but fixed contractures often develop with age
  (MGI Ref ID J:11392)
  • exhibit an arthrogryposis-like phenotype affecting the forelimbs, and in severe cases, also the hindlimbs
  (MGI Ref ID J:105260)

• decreased diameter of radius
  • radii are thinner and somewhat straighter than in controls, however gross bony landmarks and sections through bones and joints appear normal
  (MGI Ref ID J:11392)

• decreased diameter of ulna
  • ulnae are thinner and somewhat straighter than in controls
  (MGI Ref ID J:11392)

behavior/neurological phenotype

• abnormal locomotor behavior
  • develop a more pronounced waddle as grow older
  (MGI Ref ID J:11392)
  • homozygotes with bilateral forelimb abnormalities have a difficult time from a very young age in moving around the cage and slither around the cage on the undersurface of their muzzles
  (MGI Ref ID J:11392)

• abnormal maternal nurturing
  • maternal abilities are rarely good in females with severe forelimb abnormalities
  (MGI Ref ID J:11392)

• abnormal posture
  (MGI Ref ID J:105260)
  • abnormal forelimb joint postures seen within 1-2 days after birth
  (MGI Ref ID J:11392)
  • postural deformity (waiter's tip posture) of one or both forelimbs in which the fingers are flexed and the wrist and shoulder may also be flexed and the elbow rotated inward
  (MGI Ref ID J:24743)

• abnormal sexual interaction
  • males breed poorly, however females are able to breed successfully
  (MGI Ref ID J:11392)

• impaired righting response
  • unable to extend an affected forelimb above the head as part of a righting response when turned from its back onto one side
  (MGI Ref ID J:11392)

skeleton phenotype

• abnormal long bone morphology
  (MGI Ref ID J:11392)

• decreased diameter of radius
  • radii are thinner and somewhat straighter than in controls, however gross bony landmarks and sections through bones and joints appear normal
  (MGI Ref ID J:11392)

• decreased diameter of ulna
  • ulnae are thinner and somewhat straighter than in controls
  (MGI Ref ID J:11392)

muscle phenotype

• muscle phenotype
  • do not exhibit any histological abnormalities in skeletal muscle or any reductions in large limb muscle mass
  (MGI Ref ID J:11392)

nervous system phenotype

• abnormal myelination
  • cultures of primary sensory neurons fail to myelinate
  (MGI Ref ID J:208847)