Phenotypes Associated with This Genotype

Genotype
MGI:5505671

• Allelic Composition: Epg5^tm1Ygz/Epg5^tm1Ygz
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

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

Epg5^tm1Ygz/Epg5^tm1Ygz mice show motor deficits

mortality/aging

premature death ( J:196603 , J:279837 )

• male mice start to die after 10 months (J:196603)

• female mice exhibit later phenotype compared with male mice (J:196603)

• mice start to die at 10 months of age, however some survive longer (J:279837)

homeostasis/metabolism

abnormal autophagy ( J:196603 )

• impaired in neurons and glial cells, atrophic gastrocnemius (but not adductor longus and vastus medialis), adipose tissue and liver

• impaired autophagosome maturation in mouse embryonic fibroblasts

impaired autophagy ( J:279837 )

• retinas exhibit defective autophagic flux as indicated by accumulation of SQSTM1 aggregates and ubiquitin+ inclusions in the retinal ganglion layer (GCL), inner pexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE)

vision/eye

increased retina apoptosis ( J:279837 )

• photoreceptors undergo apoptotic cell death

decreased retina cone cell number ( J:279837 )

• number of cones is reduced by 15% in 5-month old mice

abnormal photoreceptor inner segment morphology ( J:279837 )

• approximate 30% reduction in inner segment and outer segment thickness at 6 months of age

• the inner segment is barely detected at 15 months

abnormal photoreceptor outer segment size ( J:279837 )

• approximate 30% reduction in inner segment and outer segment thickness at 6 months of age

• thickness of the outer segment is reduced by about 75% compared to controls at 10 months of age and is barely detected at 15 months

retina photoreceptor degeneration ( J:279837 )

• progressive photoreceptor degeneration

retina rod cell degeneration ( J:279837 )

• massive degeneration of rods

thin retina outer nuclear layer ( J:279837 )

• approximate 25% and 50% reduction in outer nuclear layer thickness at 6 and 10 months of age, respectively

• however, the number of retinal pigment epithelium cells is not reduced at 10 months of age

retina outer nuclear layer degeneration ( J:279837 )

abnormal electroretinogram waveform feature ( J:279837 )

• amplitude of the ERG response is lower in the mixed a-wave and mixed b-wave, indicating impairments in mixed rod and cone function

• mice show a reduced response in photopic tests (photopic b-wave and 30 Hz flicker), indicating impaired cone function

decreased b-wave amplitude ( J:279837 )

• amplitude of the ERG response is lower in the scotopic b-wave, indicating impairments in rod function

nervous system

microgliosis ( J:196603 )

• in the cerebrum, cerebellum and spinal cord

abnormal hippocampus morphology ( J:196603 )

• slightly irregular pattern of nerve fibers in the alveus

abnormal hippocampus pyramidal cell layer ( J:196603 )

• thin

decreased hippocampus pyramidal cell number ( J:196603 )

decreased cerebral cortex pyramidal cell number ( J:196603 )

• in layer 5 of the motor and sensory cortices

astrocytosis ( J:279837 )

• reactive astrogliosis is increased throughout the retinas, including ONL, INL, OPL, IPL and GCL

abnormal innervation ( J:196603 )

• muscle denervation progressing from hindlimb to forelimb

abnormal motor neuron morphology ( J:196603 )

• many of the remaining motor neurons are pyknotic atropic in the cortex

decreased motor neuron number ( J:196603 )

• in the anterior horn of the cervical, thoracic and lumbar spinal cord

decreased retina cone cell number ( J:279837 )

• number of cones is reduced by 15% in 5-month old mice

abnormal photoreceptor inner segment morphology ( J:279837 )

• approximate 30% reduction in inner segment and outer segment thickness at 6 months of age

• the inner segment is barely detected at 15 months

abnormal photoreceptor outer segment size ( J:279837 )

• approximate 30% reduction in inner segment and outer segment thickness at 6 months of age

• thickness of the outer segment is reduced by about 75% compared to controls at 10 months of age and is barely detected at 15 months

retina photoreceptor degeneration ( J:279837 )

• progressive photoreceptor degeneration

retina rod cell degeneration ( J:279837 )

• massive degeneration of rods

neuronal cytoplasmic inclusions ( J:196603 )

• accumulation of LC3, p62 aggregates and ubiquitin+ inclusions in the neuron and glials cells

axonal spheroids ( J:196603 )

• eosinophilic spheroids of swollen degenerating axons in the dorsal corticospinal tract of the cervical, thoracic and lumbar spinal cord

muscle

abnormal muscle fiber morphology ( J:196603 )

• vacuolated fibers at 10 months

abnormal Z line morphology ( J:196603 )

• misaligned

decreased skeletal muscle fiber size ( J:196603 )

• at 10 months

centrally nucleated skeletal muscle fibers ( J:196603 )

• at 10 months

skeletal muscle fiber degeneration ( J:196603 )

• muscle denervation and myofiber degeneration

muscular atrophy ( J:196603 )

• muscle wasting at 10 months

• irregularly shaped atrophic fibers at 10 months

behavior/neurological

poor grooming ( J:196603 )

• at 10 months

abnormal motor capabilities/coordination/movement ( J:196603 )

• stiff hindlimbs at 10 months

limb grasping ( J:196603 )

• progressively worsening

• female mice exhibit later phenotype compared with male mice

impaired coordination ( J:196603 )

• at 4 months, progressive

hindlimb paralysis ( J:196603 )

• at 10 months

• female mice exhibit later phenotype compared with male mice

adipose tissue

decreased white adipose tissue amount ( J:196603 )

• at 10 to 11 months

decreased white fat cell lipid droplet size ( J:196603 )

• smaller multilocular lipid droplets

decreased white fat cell size ( J:196603 )

growth/size/body

decreased body weight ( J:196603 )

• female mice exhibit later phenotype compared with male mice

postnatal growth retardation ( J:196603 )

cellular

increased mitochondrial size ( J:196603 )

• enlarged in muscles

abnormal autophagy ( J:196603 )

• impaired in neurons and glial cells, atrophic gastrocnemius (but not adductor longus and vastus medialis), adipose tissue and liver

• impaired autophagosome maturation in mouse embryonic fibroblasts

impaired autophagy ( J:279837 )

• retinas exhibit defective autophagic flux as indicated by accumulation of SQSTM1 aggregates and ubiquitin+ inclusions in the retinal ganglion layer (GCL), inner pexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE)

increased retina apoptosis ( J:279837 )

• photoreceptors undergo apoptotic cell death

integument

rough coat ( J:196603 )

• at 10 months

immune system

microgliosis ( J:196603 )

• in the cerebrum, cerebellum and spinal cord

liver/biliary system

liver/biliary system phenotype ( J:196603 )

N • hepatic lobular structure is normal

skeleton

kyphosis ( J:196603 )

• at 10 months

• female mice exhibit later phenotype compared with male mice

hematopoietic system

microgliosis ( J:196603 )

• in the cerebrum, cerebellum and spinal cord

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis		DOID:332	OMIM:PS105400	J:196603
retinitis pigmentosa		DOID:10584	OMIM:PS268000	J:279837