Phenotypes associated with this allele

• Allele Symbol: Hspb8^tm1Vti
• Allele Name: targeted mutation 1, Vincent Timmerman
• Allele ID: MGI:6392623
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hspb8^tm1Vti/Hspb8^tm1Vti	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl	MGI:6392628
ht2	Hspb8^tm1Vti/Hspb8^+	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl	MGI:6392827

Genotype
MGI:6392628

hm1

• Allelic Composition: Hspb8^tm1Vti/Hspb8^tm1Vti
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

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

behavior/neurological

impaired coordination ( J:284796 )

• mice show a progressive decline in locomotor performance on the rotarod from 9 months of age

• however, behavior in the hot plate test is normal

decreased grip strength ( J:284796 )

• mice show a decline in grip strength at 18 months of age

muscle

abnormal Z line morphology ( J:284796 )

• distal skeletal muscles show Z-disk disorganization

abnormal skeletal muscle fiber morphology ( J:284796 )

• gastrocnemius muscle shows increased number of myofibers with non-subsarcolemmal nuclei, a discrepancy in myofiber size, with some atrophic and several rimmed vacuoles at 9 months of age

• gastrocnemius muscle shows increased frequency of internalized nuclei, increased size variability, angulated and rounded atrophic fibers and hypertrophic fibers, clumped nuclei, rimmed vacuoles and endomysial fibrosis at 12 months of age

• aggregation of myofibril components (alphaB-crystallin, desmin, Hspb8) in muscle

skeletal muscle fiber degeneration ( J:284796 )

• severe myofiber degeneration with accumulations of electron dense granulofilamenotus material and ring fibers

muscular atrophy ( J:284796 )

• mice develop muscle atrophy with myofibrillar alterations

• muscle atrophy has a myogenic rather than neurogenic origin

myopathy ( J:284796 )

• mice show features of myofibrilliar myopathy, including severe myofiber degeneration, accumulations of electron dense granulofilamentous material and ring fibers

nervous system

abnormal sciatic nerve morphology ( J:284796 )

• mice show severe sciatic nerve axonal degeneration

• densities of large and medium myelinated axons in the distal sciatic nerve are lower in 18-month-old mice

• sciatic nerve shows Hspb8+ aggregates in 18-month-old mice

axon degeneration ( J:284796 )

• mice show progressive axonal degeneration resulting in severe sciatic nerve axonal degeneration

• severe distal axon loss in the ventral horn of the spinal cord

• distal sciatic nerves of 18-month-old mice show axonal atrophy, regenerative clusters, and infiltration by macrophages and sciatic axons show focal accumulation of mitochondria, some undergoing mitophagy, and other degenerating organelles

• clusters of axoplasmic degenerative material are more frequent in mutant sciatic axons than in wild-type axons

• however, the motoneuron bodies are spared

abnormal action potential ( J:284796 )

• mice show a reduction of the amplitude of the compound motor action potential from 6 months of age onwards

• however, nerve conduction velocities are normal

homeostasis/metabolism

impaired autophagy ( J:284796 )

• marker analysis indicates autophagy defects in muscle

• low autophagy power in the sciatic nerve

cellular

impaired autophagy ( J:284796 )

• marker analysis indicates autophagy defects in muscle

• low autophagy power in the sciatic nerve

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant distal hereditary motor neuronopathy 2		DOID:0111206	OMIM:158590	J:284796

Genotype
MGI:6392827

ht2

• Allelic Composition: Hspb8^tm1Vti/Hspb8⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

nervous system

abnormal sciatic nerve morphology ( J:284796 )

• distal sciatic nerves show regenerative clusters, macrophage infiltration, and accumulation of axoplasmic material, and myelinated Remak bundles which suggest abnormal cycles of regeneration and remyelination

muscle

abnormal muscle fiber morphology ( J:284796 )

• muscles show accumulation of electron-dense material and small and a small empty vacuole in 12-month-old mice

abnormal Z line morphology ( J:284796 )

• muscles show signs of Z-band disintegration in 12-month-old mice

behavior/neurological

behavior/neurological phenotype ( J:284796 )

N • mice do not develop motor or sensory deficits, compound motor action potential abnormalities, or axon loss