Phenotypes associated with this allele

• Allele Symbol: Uchl1^tm1Dgen
• Allele Name: targeted mutation 1, Deltagen
• Allele ID: MGI:3604452
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Uchl1^tm1Dgen/Uchl1^tm1Dgen	B6.129P2-Uchl1^tm1Dgen/Mmnc	MGI:4442972
hm2	Uchl1^tm1Dgen/Uchl1^tm1Dgen	involves: 129P2/OlaHsd * C57BL/6	MGI:3606678
cx3	Tg(Thy1-Snca)1S13Putt/0 Uchl1^tm1Dgen/Uchl1^tm1Dgen	involves: 129P2/OlaHsd * C57BL/6	MGI:5573199

Genotype
MGI:4442972

hm1

• Allelic Composition: Uchl1^tm1Dgen/Uchl1^tm1Dgen
• Genetic Background: B6.129P2-Uchl1^tm1Dgen/Mmnc

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

mortality/aging

premature death ( J:156538 )

• a few homozygous mice (6.7%) die around 1 month of age, most (81%) live up to 6 months of age; however, all die by 10 months of age and most death occurs between 7 and 10 months of age

behavior/neurological

limb grasping ( J:156538 )

• by 50 days of age mutant mice display clasping and spastic movements in their hind limbs when suspended by the tail

abnormal gait ( J:156538 )

• mutant mice exhibit a clumsy hopping gait starting at 3 months of age

forelimb paralysis ( J:156538 )

• apparent in surviving mutant mice at 8 months of age

hindlimb paralysis ( J:156538 )

• develops in mutant mice between 4 and 6 months of age

nervous system

motor neuron degeneration ( J:156538 )

• beginning at 2 months of age and progressing such that 1% of triangularis sterni muscle end-plates are denervated at 2 months of age, 2% at 3 months of age, and 28% at 5 months of age, and a similar progressive denervation is found in extensor digitorum longus muscles which have 57% of end-plates denervated by 5 months of age

• electron microscopy reveals degenerating nerve terminals wrapped by Schwann cells whose processes invade into the synaptic cleft

abnormal neuromuscular synapse morphology ( J:156538 )

• presynaptic terminals appear to retract from their corresponding end-plates beginning by 2 months of age and electron microscopy reveals a marked reduction of synaptic vesicles in the presynaptic nerve terminals with an excessive number of branched tubulovesicular profiles and multilamellar bodies

axon degeneration ( J:156538 )

• neuron degeneration appears to progress in a distal-to-proximal direction since the ventral roots are normal at 8 months of age, but the myelinated axons in their distal nerves show loss of myelinated axons by 3.5 months of age and this is more severe at 8 months of age

abnormal synaptic plasticity ( J:156538 )

increased synaptic depression ( J:156538 )

abnormal PNS synaptic transmission ( J:156538 )

abnormal endplate potential ( J:156538 )

• electrophysiologic analyses of the extensor digitorum longus shows that the end-plate potential amplitudes are significantly reduced at 3 and 5 months of age, but not significantly abnormal at 1.5 or 2 months of age, that the mean quantal content is significantly reduced at 3 and 5 months of age, and that the latencies are significantly prolonged and the rising slopes significantly decreased at 2, 3, and 5 months of age

abnormal miniature endplate potential ( J:156538 )

• electrophysiologic analyses of the extensor digitorum longus shows that, although the mEPP amplitide is unaffected, by 2 months of age, and also at 3 and 5 months of age, mEEP frequencies are significantly reduced, indicative of a presynaptic defect resulting in impaired spontaneous synaptic transmission through the neuromuscular junction

decreased neurotransmitter release ( J:156538 )

• the decreased end-plate potential and quantal content along with normal acetylcholine receptor staining indicate diminshed neurotransmitter release at the neuromuscular junction

decreased paired-pulse facilitation ( J:156538 )

• at two months of age paired-pulse depression is found in neuromuscular junctions rather than normal paired-pulse facilitation and the rate of end-plate potential rundown increases with age and amplitude

skeleton

kyphosis ( J:156538 )

• apparent at 3 months of age

Genotype
MGI:3606678

hm2

• Allelic Composition: Uchl1^tm1Dgen/Uchl1^tm1Dgen
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

behavior/neurological

increased coping response ( J:101679 )

• exhibit a significant decrease in time immobile during tail suspension testing, which may be associated with a decreased depression-like state

impaired coordination ( J:101679 , J:207278 )

• exhibit a significant decrease in motor performance on the rotarod test, falling from the rotarod at significantly slower speeds than wildtype (J:101679)

• mice start to show motor deficits on the rotating beam by 2.5 months of age (J:207278)

decreased grip strength ( J:207278 )

• muscle weakness is apparent at 4.5 months of age but not at 2.5 months of age

increased thermal nociceptive threshold ( J:101679 )

• exhibit a significant increase in thermal response latency during hot plate testing

growth/size/body

weight loss ( J:207278 )

• mice start to show a slight weight loss by 2.5 months of age

Genotype
MGI:5573199

cx3

• Allelic Composition: Tg(Thy1-Snca)1S13Putt/0; Uchl1^tm1Dgen/Uchl1^tm1Dgen
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:207278 )

• at 3.5 months of age, mutants need to be sacrificed due to poor health

nervous system

astrocytosis ( J:207278 )

• mice show a large increase in astrogliosis at 3.5 months of age compared to single Tg(Thy1-Snca)1S13Putt mutants, especially in the cortex and to a lesser extent in the hippocampus and the striatum, but not in the cerebellum, brainstem, and thalamus

• 3.5 month old mice however, do not show microgliosis or axon degeneration

alpha-synuclein inclusion body ( J:207278 )

• increase in perikaryal alpha-synuclein accumulation in the cell soma of hippocampal neurons at 3.5 months of age

behavior/neurological

impaired coordination ( J:207278 )

• mice show greater deficits in motor coordination on the rotarod than single Uchl1 homozygotes at 2.5 months of age

decreased grip strength ( J:207278 )

• mice show greater deficits in muscle strength than single Uchl1 homozygotes at 2.5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:207278