Phenotypes associated with this allele

• Allele Symbol: Dst^Tg4
• Allele Name: transgene insertion 4
• Allele ID: MGI:1856421
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dst^Tg4/Dst^Tg4	involves: C57BL/6 * CD-1	MGI:5577168
hm2	Dst^Tg4/Dst^Tg4	involves: CD-1	MGI:3616962
ht3	Dst^Tg4/Dst^+	involves: CD-1	MGI:3616983

Genotype
MGI:5577168

hm1

• Allelic Composition: Dst^Tg4/Dst^Tg4
• Genetic Background: involves: C57BL/6 * CD-1

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

mortality/aging

postnatal lethality ( J:209161 )

• mice die at around P20

growth/size/body

slow postnatal weight gain ( J:209161 )

• at around 2 weeks of age, mice show an arrest in weight-gain

behavior/neurological

limb grasping ( J:209161 )

• hind limb clasping is seen at P15 or earlier

impaired coordination ( J:209161 )

• mice fall off a beam and are unable to effectively balance and/or grip to remain on the suspended beam

abnormal gait ( J:209161 )

• at around 2 weeks of age, mice show ambulating abnormalities and at P20, mice exhibit an aberrant gait

nervous system

abnormal muscle spindle morphology ( J:209161 )

• degeneration of muscle spindles in tibialis anterior muscles

abnormal axon morphology ( J:209161 )

• microtubule network is disorganized, with an accumulation of beta-III tubulin throughout axons

abnormal sensory neuron morphology ( J:209161 )

• dilated rough ER sheets and Golgi membranes in P5 sensory neurons

abnormal neuromuscular synapse morphology ( J:209161 )

• increase in the number of immature endplates and neuromuscular junctions in muscles

neuron degeneration ( J:209161 )

• sensory neuron degeneration begins at P15

abnormal dorsal root ganglion morphology ( J:209161 )

• dorsal sensory roots are smaller, have fewer axons, axons undergoing degeneration and axonal swellings

small dorsal root ganglion ( J:209161 )

axon degeneration ( J:209161 )

• dorsal sensory roots show axons undergoing degeneration

immune system

conjunctivitis ( J:209161 )

• P20 mice occasionally exhibit conjunctivitis

muscle

abnormal muscle spindle morphology ( J:209161 )

• degeneration of muscle spindles in tibialis anterior muscles

vision/eye

conjunctivitis ( J:209161 )

• P20 mice occasionally exhibit conjunctivitis

blepharoptosis ( J:209161 )

• P20 mice occasionally exhibit blepharoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary sensory neuropathy		DOID:0050548	OMIM:PS162400	J:209161

Genotype
MGI:3616962

hm2

• Allelic Composition: Dst^Tg4/Dst^Tg4
• Genetic Background: involves: CD-1

mortality/aging

postnatal lethality ( J:17844 )

• most die before weaning or shortly thereafter

behavior/neurological

impaired limb coordination ( J:17844 )

• begin to show signs of limb incoordination at around 10-12 days after birth and then show progressive loss of coordination

nervous system

abnormal Schwann cell morphology ( J:48174 )

• primary cultures of Schwann cells from the sciatic nerve have morphological abnormalities, although they are milder than those of homozygous Dst^dt-27J mice

abnormal axon morphology ( J:48174 )

• reduction in the axonal caliber in the peripheral nerves

abnormal myelin sheath morphology ( J:48174 )

• reduction in myelin sheath thickness in the peripheral nervous system

abnormal sensory neuron morphology ( J:47356 )

• progressive sensory neuron degeneration that begins by E15.5

abnormal glossopharyngeal ganglion morphology ( J:104592 )

• 70% reduction in vagal and glossopharyngeal sensory neurons

abnormal vagus nerve morphology ( J:104592 )

• 70% reduction in vagal and glossopharyngeal sensory neurons

abnormal dorsal root ganglion morphology ( J:91495 )

• cultured dorsal root ganglia neurons are capable of forming neurites, however the neurofilament and microtubule network is disorganized in the neurites

abnormal dorsal spinal root morphology ( J:17844 , J:47356 )

• severe loss of dorsal spinal root sensory axons at all levels of the spinal cord, however ventral motor roots are unaffected (J:17844)

• dorsal roots are small, contain few axon profiles and few myelinated fibers, have an abundance of denervated Schwann cells, and occasionally see a giant axon profile (J:17844)

• cytoskeletal network of dorsal root axons is perturbed, with disorganized intermediate filament and microtubule networks (J:47356)

peripheral nervous system degeneration ( J:47356 )

• sensory neuron degeneration begins by E15.5 and progresses gradually, continuing through the rest of embryogenesis and postnatal development

abnormal nervous system physiology ( J:48174 )

abnormal myelination ( J:17844 , J:48174 )

• dorsal root axons contain few myelinated fibers (J:17844)

• abnormal myelination in the peripheral nervous system, but not in the central nervous system, with hypomyelination of the ventral and dorsal roots and some rare amyelinated axons (J:48174)

craniofacial

abnormal circumvallate papillae morphology ( J:104592 )

• 45% reduction in size of the circumvallate papilla

abnormal gustatory papilla taste bud morphology ( J:104592 )

• 89% reduction in the number of taste buds

• decrease in the number of PGP 9.5-, CGRP-, P2X3- and tyrosine hydroxylase-containing neurons and their peripheral endings in the taste bud and epithelium

digestive/alimentary system

abnormal circumvallate papillae morphology ( J:104592 )

• 45% reduction in size of the circumvallate papilla

abnormal gustatory papilla taste bud morphology ( J:104592 )

• 89% reduction in the number of taste buds

• decrease in the number of PGP 9.5-, CGRP-, P2X3- and tyrosine hydroxylase-containing neurons and their peripheral endings in the taste bud and epithelium

growth/size/body

abnormal circumvallate papillae morphology ( J:104592 )

• 45% reduction in size of the circumvallate papilla

abnormal gustatory papilla taste bud morphology ( J:104592 )

• 89% reduction in the number of taste buds

• decrease in the number of PGP 9.5-, CGRP-, P2X3- and tyrosine hydroxylase-containing neurons and their peripheral endings in the taste bud and epithelium

taste/olfaction

abnormal gustatory papilla taste bud morphology ( J:104592 )

• 89% reduction in the number of taste buds

• decrease in the number of PGP 9.5-, CGRP-, P2X3- and tyrosine hydroxylase-containing neurons and their peripheral endings in the taste bud and epithelium

cellular

abnormal skeletal muscle fiber mitochondrial morphology ( J:55704 )

• accumulation and abnormal distribution of mitochondria in skeletal muscle

muscle

abnormal Z line morphology ( J:55704 )

• Z disks from muscle fibers appear thicker

abnormal skeletal muscle fiber morphology ( J:55704 )

• P3 skeletal muscle fibers show regionalized collapse of cytoarchitecture

• accumulation of mitochondria at the periphery of muscle fibers in P3 and adult mice

• myoblasts fuse to form myotubes in culture, however, terminally differentiated myotubes contain incompletely assembled myofibrils

• myotubes that form from primary myoblast cultures show abnormal distribution of mitochondria, and contain fewer myofibrils with incomplete assembly as indicated by absence of Z-disk material

abnormal skeletal muscle fiber mitochondrial morphology ( J:55704 )

• accumulation and abnormal distribution of mitochondria in skeletal muscle

abnormal muscle physiology ( J:55704 )

• diaphragm muscle is susceptible to contraction-induced sarcolemmal damage

impaired skeletal muscle contractility ( J:55704 )

• myotubes that form from primary myoblast cultures exhibit only weak contractions, show abnormal distribution of mitochondria, and contain fewer myofibrils with incomplete assembly as indicated by absence of Z-disk material

muscle weakness ( J:55704 )

• isometric contractility measurements show that the diaphragm muscle is weak

Genotype
MGI:3616983

ht3

• Allelic Composition: Dst^Tg4/Dst⁺
• Genetic Background: involves: CD-1

nervous system

abnormal Schwann cell morphology ( J:48174 )

• frequently observe double myelin figures within the same Schwann cell cytoplasm

abnormal axon morphology ( J:48174 )

• reduction in the axonal caliber in peripheral nerves

abnormal myelination ( J:48174 )

• abnormal myelination of peripheral nerves, with some ventral root axons appearing hypermyelinated relative to their axonal caliber and about 4% of small caliber axons amyelinated, however heterozygotes do not present any behavioral phenotypes or sensory neuron degeneration