About   Help   FAQ
Phenotypes Associated with This Genotype
Genotype
MGI:3614946
Allelic
Composition
Vps54wr/Vps54wr
Genetic
Background
multiple strains
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Vps54wr mutation (3 available); any Vps54 mutation (284 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• very reduced viability

growth/size/body
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
• upward pointed snout
• at 30 days of age (J:1563)
• 47% normal (J:1563)

behavior/neurological
• unusual clasping of feet when suspended by tail (J:6388)
• fine tremors of the head (J:5102)
• in forepaws
• muscle weakness by fourth or fifth week
• head and anterior trunk held lower than normal
• by 30 days of age (J:1563)
• high stepping and unsteady (J:5102)
• eventually walk on dorsum of forepaws due to the inability to extend the paws at the wrist (J:5102)
• ultimately they push the body along using their hind legs only (J:5102)
• paralysis primarily affects forelimbs (J:165)
• clasping of front paws and difficulties using front legs (J:1563)

nervous system
• brain stem and spinal cord through the thoracic region weighs 62-68% of controls
• cross section area of spinal cord 75-80% of normal
• small numbers of GFAP positive cells in the anterior horn of the spinal cord at 1 month of age and found throughout the gray matter by 10 months
• astrocyte processes perpendicular to surface of cord rather than parallel as in controls
• GFAP reactive material gradually increases from 2 to 5 months of age
• hypertrophy
• eccentric nuclei (J:5102)
• enlarged soma (J:19087)
• poorly stained Nissl bodies (J:19087)
• reduced numbers of dendrites (J:19087)
• in brain stem and spinal cord but not basal ganglia or cerebral cortex (J:5102)
• progressive denervation of skeletal muscle (J:5102)
• sprouting from myelinated part of preterminal axons and nerve fibers innervate several muscle fibers (J:5102)
• reduced numbers of motor nerves in affected muscle (J:5102)
• vacuolated neurons develop in the cervical spinal cord with much larger surface areas in x-section and smaller nuclear areas (J:6238)
• normal neurons are smaller in x-section but with normal nuclear areas (J:6238)
• protein synthesis reduced in both types of neurons (J:6238)
• vacuolar degeneration of motoneurons also in the lower brain stem (cerebellar, reticular, vestibular, cortical, and olfactory involvement variable) (J:6388)
• number of degenerating neurons increases with development of disease, none before onset of symptoms (J:19087)
• loss of large diameter nerve fibers in the median nerve
• loss of large diameter nerve fibers
• numbers of myelinated nerve fibers in the nerves to the arm and in the nerve to the tibialis anterior muscle were reduce 67-82%
• in conjunction with dissolution of axoplasm and nerve degeneration
• impaired slow axonal transport affecting neurofilament proteins more than tubulin and actin (J:8186)
• fast axonal transport rate reduced 25% (J:14361)
• levels of thyrotropin releasing hormone in the cervical spinal cord increase with progression of disease (J:3719)
• early increases in substance P in the hypothalamus, later increases in spinal cord and midbrain (J:3719)
• variable levels of Met- and Leu-enkephalin over the course of disease progression (J:3719)
• greater numbers of thyrotrophin releasing hormone neuronal processes in the ventrolateral horn of the spinal cord but decreasing with age (J:15226)
• reduced acetylcholinesterase containing cells in the ventral horn of the spinal cord (J:35070)
• substance P elevated in the ventral horn of the spinal cord early but becoming less as the disease progresses (J:35070)

muscle
• enlargement of sarcolemmal nuclei which migrate to the center of the muscle fiber
• muscle fibers eventually decrease in diameter
• deposition of fat between atrophied muscle fibers
• lose of ability to extend paws at wrist (J:5102)
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back (J:5102)
• muscle atrophy seen by 6-7 weeks of age (J:5102)
• neurogenic atrophy seen in muscles of mastication, neck, shoulder girdle, and intercostals (J:6388)
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
• by fourth or fifth week
• particularly involves forelimbs

reproductive system
• sperm motility reduced to occasional trembling of the tail
• testis weight 72% of normal
• sperm numbers 70-80% of controls
• lack of intact acrosome
• round sperm heads
• both sexes sterile (J:165)

homeostasis/metabolism
• decreased levels in both sexes
• cGMP levels decreased 80% in cervical spinal cord, 56% in the cerebellum, and 29% in the cortex

craniofacial
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
• upward pointed snout

liver/biliary system
• vacuolar changes in hepatocytes

cellular
• all in degenerating neurons
• increase in randomly organized neuronal cytoplasmic microtubules, filaments or smooth endoplasmic reticulum
• membrane bound dense bodies and /or lipid droplets
• sperm numbers 70-80% of controls
• lack of intact acrosome
• round sperm heads
• reduction and disorganization of rough endoplasmic reticulum
• increased numbers of lysosomes and autophagic vacuoles
• sperm motility reduced to occasional trembling of the tail

endocrine/exocrine glands
• testis weight 72% of normal

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Werdnig-Hoffmann disease DOID:13137 OMIM:253300
J:6388


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
Citing These Resources
Funding Information
Warranty Disclaimer, Privacy Notice, Licensing, & Copyright
Send questions and comments to User Support.
last database update
10/29/2024
MGI 6.24
The Jackson Laboratory