Phenotypes associated with this allele

• Allele Symbol: Uchl1^gad
• Allele Name: gracile axonal dystrophy
• Allele ID: MGI:1856882
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Uchl1^gad/Uchl1^gad	involves: CBA/Nga * RFM/Nga	MGI:3038456
hm2	Uchl1^gad/Uchl1^gad	Not Specified	MGI:3038779
cx3	Uchl1^gad/Uchl1^gad Uchl3^tm1Tilg/Uchl3^tm1Tilg	involves: 129S1/Sv * C57BL/6J * CBA/Nga * RFM/Nga	MGI:3758072

Genotype
MGI:3038456

hm1

• Allelic Composition: Uchl1^gad/Uchl1^gad
• Genetic Background: involves: CBA/Nga * RFM/Nga

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

mortality/aging

premature death ( J:30954 , J:71819 )

• death by 5 or 6 months (J:30954)

• paralysis interferes with feeding leading to starvation, with complete mortality by ~250 days; mena survival is 187 days (J:71819)

behavior/neurological

tremors ( J:30954 )

• beginning after ataxia and progressively more severe with age

ataxia ( J:30954 , J:71819 )

• beginning at 80 days of age and progressively more severe with age (J:30954)

• 100% of mice develop sensory ataxia by ~80 days (J:71819)

abnormal stationary movement ( J:30954 )

• difficulty moving, beginning after ataxia and progressively more severe with age

• eventually immobile

abnormal gait ( J:71819 )

• both hindlimb digits and footpads make contact when walking, whereas only digits make contact when wild-type mice walk

paralysis ( J:71819 )

• eventually mice become paralyzed

cardiovascular system

cardiovascular system phenotype ( J:30954 )

N • heart appeared normal macro- and micro-scopically

digestive/alimentary system

digestive/alimentary phenotype ( J:30954 )

N • intestine appeared normal macro- and micro-scopically

growth/size/body

decreased body weight ( J:71819 )

• weight is 20% less than wild-type by 80 days of age

weight loss ( J:30954 )

• after appearance of ataxia

hematopoietic system

hematopoietic system phenotype ( J:30954 )

N • spleen appeared normal macro- and micro-scopically

limbs/digits/tail

abnormal hindlimb morphology ( J:30954 )

• atrophy, evident after onset of ataxia, and progressing to anterior part of body

liver/biliary system

liver/biliary system phenotype ( J:30954 )

N • liver appeared normal macro- and micro-scopically

renal/urinary system

renal/urinary system phenotype ( J:30954 )

N • kidney appeared normal macro- and micro-scopically

respiratory system

respiratory system phenotype ( J:30954 )

N • lung appeared normal macro- and micro-scopically

nervous system

abnormal medulla oblongata morphology ( J:30954 )

• axon degeneration in the gracile nucleus

abnormal dorsal root ganglion morphology ( J:71819 )

• 2.2-fold increase in number of small basophilic DRG cell bodies

abnormal spinal cord dorsal column morphology ( J:30954 )

• axon degeneration in the gracile fascicules

axon degeneration ( J:30954 )

• in the gracile nucleus of the medulla oblongata and the gracile fascicules of the spinal cord

axonal dystrophy ( J:71819 )

• a low level of dystrophic axonal dystrophy is observed in nucleus tractus solitarus and area postrema

Genotype
MGI:3038779

hm2

• Allelic Composition: Uchl1^gad/Uchl1^gad
• Genetic Background: Not Specified

nervous system

motor neuron degeneration ( J:28526 )

• axonal degeneration occurred first at motor nerve terminals in the distal end plate zone, and extended gradually from distal to proximal parts of affected axons in intramuscular nerve trunk

axon degeneration ( J:28526 )

• axonal degeneration occurred first at motor nerve terminals in the distal end plate zone, and extended gradually from distal to proximal parts of affected axons in intramuscular nerve trunk

Genotype
MGI:3758072

cx3

• Allelic Composition: Uchl1^gad/Uchl1^gad; Uchl3^tm1Tilg/Uchl3^tm1Tilg
• Genetic Background: involves: 129S1/Sv * C57BL/6J * CBA/Nga * RFM/Nga

mortality/aging

premature death ( J:71819 )

• mortality resulting from starvation occurs, with all mice succumbing by ~200 days, with mean survival of 118 days

growth/size/body

decreased body weight ( J:71819 )

• by 80 days of age, mice weigh 45% less than wild-type and 30% less than single homozgyotes by 80 days of age

nervous system

abnormal dorsal root ganglion morphology ( J:71819 )

• DRG cell bodies from which the gracile axons emanate show increased degeneration, with smaller cell diameter and more basophilic cytoplasm; abnormal cell morphology is 4.1-fold higher than in wild-type

axon degeneration ( J:71819 )

• more severe than Uchl1^gad homozygotes

axonal dystrophy ( J:71819 )

• at ~90 days of age, dystrophic axons or spheroids are observed in sections of gracile nucleus

• increased numbers of spheroids are seen in double mutants compared to Uchl-null mice in nucleus tractus solitarus and area postrema; increase is seen in gracile nucleus of the medulla and in the gracile fascicle of the spinal cord at cervical and thoracic levels

behavior/neurological

dysphagia ( J:71819 )

• occurs with high penetrance compared to single homozygotes; associated with terminal stages and range from several days to several weeks in duration

ataxia ( J:71819 )

• 100% of mice develop sensory ataxia by ~80 days

abnormal gait ( J:71819 )

• both hindlimb digits and footpads make contact when walking ('flatfooted'), whereas only digits make contact when wild-type mice walk

paralysis ( J:71819 )

• at time of death, mice display only moderate posterior paralysis compared to more severely affected age-matched Uchl1^gad mutants

digestive/alimentary system

dysphagia ( J:71819 )

• occurs with high penetrance compared to single homozygotes; associated with terminal stages and range from several days to several weeks in duration