growth/size/body region phenotype

• decreased body weight
  • at 28 days of age the average weight of males, 6.3g, is less than half that of normal controls, 14.2g
  (MGI Ref ID J:2856)

nervous system phenotype

• optic nerve degeneration
  • at 28 days of age there is primary axonal degeneration of the optic nerve, but significant dysmyelination or hypomyelination are not found in the optic nerves at this timepoint
  (MGI Ref ID J:2856)

vision/eye phenotype

• optic nerve degeneration
  • at 28 days of age there is primary axonal degeneration of the optic nerve, but significant dysmyelination or hypomyelination are not found in the optic nerves at this timepoint
  (MGI Ref ID J:2856)

homeostasis/metabolism phenotype

• hypoglycemia
  • mice are hypoglycemic from 20 days until death
  (MGI Ref ID J:14851)

• abnormal enzyme/coenzyme level
  • liver homogenates have decreased phenylalanine hydroxylase activity, decreased phenylalanine-sodium pyruvate transaminase activity, and increased phenylalanine-alpha-ketoglutarate transaminase activity, increased tyrosine-alpha-ketoglutarate transaminase activity, increased tryptophan-alpha-ketoglutarate activity, and increased tryptophan pyrrolase activity
  (MGI Ref ID J:5108)
  • activity, increased tryptophan-alpha-ketoglutarate activity, and increased tryptophan pyrrolase activity
  (MGI Ref ID J:5108)

• increased circulating tyrosine level
  • me progressively lower to 26 days of age (14.13 ug/ml vs 22.18 ug/ml in heterozygotes), although loading experiments show that homozygotes handle added tyrosine and tryptophan in a manner comparable to that of heterozygous littermates
  (MGI Ref ID J:5108)
  • plasma tyrosine concentration is higher than normal at 14 days of age then rapidly drops to abnormally low levels (at 26 days of age 13.36 ug/ml vs 23.12 ug/ml in heterozygotes) and plasma tryptophan levels are lower than normal at 14 days of age and become progressively lower to 26 days of age (14.13 ug/ml vs 22.18 ug/ml in heterozygotes), although loading experiments show that homozygotes handle added tyrosine and tryptophan in a manner comparable to that of heterozygous littermates
  (MGI Ref ID J:5108)

• abnormal circulating amino acid level
  • plasma phenylalanine concentration rises after 18 days of age to abnormally high levels and phenylalanine loading experiments show that at 22 days of age homozygotes can not normally metabolize exogenous phenylalanine, although they can at 14 days of age
  (MGI Ref ID J:5108)

mammalian phenotype

• hearing/vestibular/ear phenotype
  • Normal - normal hearing and auditory reflexes
  (MGI Ref ID J:15162)

• behavior/neurological phenotype
  • Normal - can orient in water and swim
  (MGI Ref ID J:13068)

• nervous system phenotype
  • Normal - demyelination is not found in the telencephalon at 2.5 weeks of age
  (MGI Ref ID J:13068)
  • Normal - there is no myelin degeneration detected in the thalamus
  (MGI Ref ID J:15162)

mortality/aging

• lethality at weaning, complete penetrance
  • most homozygotes die by wean age, with males dying at approximately 3 weeks of age and females dying approximately a week later
  (MGI Ref ID J:13068)

nervous system phenotype

• demyelination
  • body, the lateral lemniscus, brachium conjunctivum, red nucleus, and the rubrospinal and tectospinal tracts
  (MGI Ref ID J:15162)
  • eks of age very severe demyelination is found throughout the archi- and paleocerebellar systems, with heavy degeneration permeating the vestibulo-spinal tract, dorsal spinocerebellar tract, brachium conjunctivum, magnocellular red nucleus, rubrospinal tra
  (MGI Ref ID J:13068)
  • ct, vestibular nerve and nuclei, juxtarestiform body, trapezoid body and the superior olivary nucleus, and moderate degeneration in the medial lemnicus, medial longitudinal fasiculus and tecto-spinal tracts
  (MGI Ref ID J:13068)
  • at one week of age a small amount of myelin degeneration can be found in the ventral funiculus of the spinal cord; at two weeks of age myelin degeneration is marked in the vestibulo-spinal tracts and beginning in the spino-cerebellar tracts; and by 2.5 weeks of age very severe demyelination is found throughout the archi- and paleocerebellar systems, with heavy degeneration permeating the vestibulo-spinal tract, dorsal spinocerebellar tract, brachium conjunctivum, magnocellular red nucleus, rubrospinal tract, vestibular nerve and nuclei, juxtarestiform body, trapezoid body and the superior olivary nucleus, and moderate degeneration in the medial lemnicus, medial longitudinal fasiculus and tecto-spinal tracts
  (MGI Ref ID J:13068)
  • in the vestibulosponal tract from the lateral vestibular nucleus to the spinal cord, and in the entering fibers of the eighth cranial nerve, the juxtaresiform body, the medullary center of the cerebellum, the medial longitudinal fasciculus, the trapezoid body, the lateral lemniscus, brachium conjunctivum, red nucleus, and the rubrospinal and tectospinal tracts
  (MGI Ref ID J:15162)

behavior/neurological phenotype

• ataxia
  (MGI Ref ID J:15162)
  • homozygotes have difficulty in walking and when trying to walk seem to pull the hind feet along rather than pushing off with them
  (MGI Ref ID J:13068)

• tremors
  (MGI Ref ID J:13068)

• limb grasping
  • when homozyogtes are lifted by the tail, the hind feet lock together in a spasm
  (MGI Ref ID J:13068)

• abnormal gait
  (MGI Ref ID J:13068)

• abnormal reflex
  • no reaction to pinching of the tail
  (MGI Ref ID J:13068)

• abnormal motor coordination/balance
  • swaying of the body, dragging of the hind limbs and progressive incoordination of the limbs when walking
  (MGI Ref ID J:15162)

• impaired limb coordination
  (MGI Ref ID J:15162)

behavior/neurological phenotype

• ataxia
  • mild ataxia is characterized by the hind feet going out to the side more than normal and the body being closer to the ground
  (MGI Ref ID J:13068)
  • Background Sensitivity - heterozygous mice are distinguishable from normal mice only in exceptional cases
  (MGI Ref ID J:270)

• abnormal motor coordination/balance
  • symptoms are subtle and obvious only to experienced observers
  (MGI Ref ID J:13068)
  • all heterozygotes are not symptomatic
  (MGI Ref ID J:13068)

nervous system phenotype

• demyelination
  • moderate demyelination restricted to the vestibulospinal tract
  (MGI Ref ID J:15162)
  • at 2 weeks of age a small amount of myelin degeneration is found in the vestibulo-spinal tract and at 2.5 weeks myelin degeneration is still confined to the vestibulo-spinal pathway with the cerebellar systems unaffected
  (MGI Ref ID J:13068)

behavior/neurological phenotype

• decreased startle reflex
  (MGI Ref ID J:211318)

hearing/vestibular/ear phenotype

• increased or absent threshold for auditory brainstem response
  • at 2 months
  (MGI Ref ID J:211318)

mammalian phenotype

• vision/eye phenotype
  • Normal - outer segment photoreceptors exhibit normal morphology
  (MGI Ref ID J:211318)

• hearing/vestibular/ear phenotype
  • Normal - outer and inner hair cells appear normal
  (MGI Ref ID J:211318)

nervous system phenotype

• cochlear ganglion degeneration
  • at 2 months
  (MGI Ref ID J:211318)

• short photoreceptor outer segment
  • at P30 and P60
  (MGI Ref ID J:211318)

• decreased retinal photoreceptor cell number
  • at P30 and P60
  (MGI Ref ID J:211318)

vision/eye phenotype

• decreased retinal photoreceptor cell number
  • at P30 and P60
  (MGI Ref ID J:211318)

• short photoreceptor outer segment
  • at P30 and P60
  (MGI Ref ID J:211318)