Phenotypes associated with this allele
Allelic
Composition |
Hexbtm1Rlp/Hexbtm1Rlp
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Genetic
Background |
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hexbtm1Rlp mutation
(1 available);
any
Hexb mutation
(91 available)
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Hexbtm1Rlp/Hexbtm1Rlp mice exhibit Sandhoff disease phenotypes that are improved in Hexbtm1Rlp/Hexbtm1Rlp Ccl3tm1Unc/Ccl3tm1Unc mice
mortality/aging
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• survival to about 102 days of age
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immune system
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• elevated circulating antibody levels
• IgG deposition on the surface of neurons
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• Il4 levels in serum are elevated after 14 weeks of age
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• peripheral phagocytes start appearing in the CNS after 3 months of age
• found foamy cells characteristic of macrophage found in the CNS at 4 months as are amoeboid brain macrophage
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behavior/neurological
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• wide-opening stance of hind limbs
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adipose tissue
muscle
nervous system
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• increased apoptosis in the thalamus
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• peripheral phagocytes start appearing in the CNS after 3 months of age
• found foamy cells characteristic of macrophage found in the CNS at 4 months as are amoeboid brain macrophage
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cellular
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• increased apoptosis in the thalamus
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homeostasis/metabolism
hematopoietic system
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• elevated circulating antibody levels
• IgG deposition on the surface of neurons
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|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hexbtm1Rlp mutation
(1 available);
any
Hexb mutation
(91 available)
|
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Spinal cord pathology comparison of Hexbtm1Rlp/Hexbtm1Rlp B4galnt1tm1Rlp/B4galnt1tm1Rlp and Hexbtm1Rlp/Hexbtm1Rlp mice
mortality/aging
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• died around 120 to 150 days of age
(J:53080)
• average life span of 127 days
(J:190450)
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behavior/neurological
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• beginning at 3 months and progressing with age
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• progressive loss of righting response with age
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• performance in a rotarod test is impaired at 9 weeks and declines very rapidly after 11 weeks of age
• at 16 weeks of age, homozygous mice are unable to stay on a rotarod
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• spastic movements of hind limbs starting around 5 months
• near lack of hind limb movement by 5 months and fore limbs also afflicted
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nervous system
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• neuronal storage vacuoles (PAS positive) found throughout the central nervous system
• vacuoles very abundant in anterior horn motor neurons of the spinal cord
• PAS positive granules also found in neuropil and dendrites
• no granules found in cerebral and cerebellar white matter, nerve fiber tracts, spinal roots or optic nerves
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muscle
liver/biliary system
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• storage vacuoles found in cells in hepatic sinusoids
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• PAS positive storage vacuoles found
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renal/urinary system
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• storage vacuoles found in epithelial cells of the proximal tubules
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growth/size/body
Allelic
Composition |
Hexbtm1Rlp/Hexb+
|
|
Genetic
Background |
involves: 129S4/SvJae * C57BL/6 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hexbtm1Rlp mutation
(1 available);
any
Hexb mutation
(91 available)
|
|
|
mortality/aging
|
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• heterozygotes died at 149-184 days of age
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mortality/aging
|
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• survival to about 130 days of age
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homeostasis/metabolism
immune system
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• slightly elevated circulating antibody levels but less than in singly homozygous Hexbtm1Rlp
|
behavior/neurological
|
N |
• able to open their limbs and move actively when lifted by their tails
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• improved coordination in a rotarod test relative to singly homozygous Hexbtm1Rlp until 12 weeks of age when deteriorating performance is seen
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nervous system
|
N |
• minimal Purkinje cell degeneration
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cellular
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• reduced apoptosis in the brain relative to singly homozygous Hexbtm1Rlp
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hematopoietic system
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• slightly elevated circulating antibody levels but less than in singly homozygous Hexbtm1Rlp
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Hexbtm1Rlp/Hexbtm1Rlp mice exhibit Sandhoff disease phenotypes that are improved in Hexbtm1Rlp/Hexbtm1Rlp Ccl3tm1Unc/Ccl3tm1Unc mice
mortality/aging
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• life span of approximately 156 days (maximum 175 days)
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behavior/neurological
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• improved performance on a rotarod compared to mice homozygous for the Hexb allele alone
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• improved relative to mice homozygous for the Hexb allele alone
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growth/size/body
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N |
• maintained body weight through 19 weeks of age
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immune system
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• 87% reduction of TNF alpha in the spinal cord relative to levels seen in mice homozygous only for Hexbtm1Rlb
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• fewer cells infiltrating the CNS of 4 month old mice
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cellular
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N |
• near absence of apoptosis in the central nervous system
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nervous system
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• fewer cells infiltrating the CNS of 4 month old mice
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homeostasis/metabolism
mortality/aging
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• life span of approximately 138 day
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behavior/neurological
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• improved performance on a rotarod compared to mice homozygous for the Hexb allele alone
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• improved relative to mice homozygous for the Hexb allele alone
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Hexbtm1Rlp/Hexbtm1Rlp B4galnt1tm1Rlp/B4galnt1tm1Rlp mice have a hunched posture and are disheveled compared to B4galnt1tm1Rlp/B4galnt1tm1Rlp mice
mortality/aging
|
N |
• most mice survive past 300 days of age
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behavior/neurological
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• ataxic gait beginning around 7 months
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• rotarod performance impaired but stable through time
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nervous system
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• fine to coarse vacuoles in the cell bodies of neurons
• vacuoles are relatively empty with relatively little electron dense material
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• accumulate abnormal amounts of oligosaccharide
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• extensive loss of cerebellar purkinje cells by 8.5 months of age
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hematopoietic system
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• vacuolated macrophage found in liver, spleen and kidney
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renal/urinary system
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• vacuolated epithelial cells
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reproductive system
endocrine/exocrine glands
immune system
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• vacuolated macrophage found in liver, spleen and kidney
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behavior/neurological
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• impaired righting reflexes seen at 23 weeks of age
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• progressive impairment of rotorod performance
• becoming worse than double homozygotes by 21 weeks of age
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mortality/aging
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• life span of 1-4 months
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behavior/neurological
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• decline in motor functions begins before 3 months of age
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• impaired performance in a rotarod test is significantly greater than in either singly homozygous mouse
• poor performance in a "wire hang" test
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• decreased horizontal activity
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nervous system
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• vacuolated macrophage found throughout the central nervous
system
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• swollen cell bodies in all neurons of the brain, trigeminal ganglia, and dorsal root ganglia
• storage cells in addition to neurons found througout the central nervous system and peripheral nerves
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• hypomyelination of the corpus callosum was seen with some myelination seen in the posterior third
• more moderate mypomyelination seen in the cerebellar white matter, brain stem and spinal cord
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homeostasis/metabolism
craniofacial
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• chalky white, unusually thickened and brittle by 4 to 4.5 months of age
(J:41920)
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• frontal bossing of the skull
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skeleton
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• chalky white, unusually thickened and brittle by 4 to 4.5 months of age
(J:41920)
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• frontal bossing of the skull
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• articular cartilage of ribs with enlarged and vacuolated chondrocytes
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• abnormally shaped rib cage
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• articular cartilage of vertebrae with enlarged vacuolated chondrocyte
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• boney trabeculae are thickened and irregular
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vision/eye
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• vacuolated macrophage found in the eye
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hearing/vestibular/ear
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• unresponsive to sharp noises
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growth/size/body
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• frontal bossing of the skull
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• indistinguishable at birth but smaller in size by 4-5 weeks
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reproductive system
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• do not breed successfully
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renal/urinary system
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• elevated levels of some monosaccharides in urine
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• glycosaminoglycan fragments in urine are elevated 50-fold
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limbs/digits/tail
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• feet thickened with flexion contractures of digits
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|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hexbtm1Rlp mutation
(1 available);
any
Hexb mutation
(91 available)
Tg(Hexb-tTA2S,tetO-Hexb)#Tjsa mutation
(0 available)
|
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Localized glycolipid storage and microgliosis in Hexbtm1Rlp/Hexbtm1Rlp Tg(Hexb-tTA2S,tetO-Hexb)#Tjsa/0 mice
mortality/aging
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• at 6 months of age mice do not show overt signs of disease but deteriorate rapidly after this
• average life span of 373 to 404 days
• when given doxycycline starting at 5 weeks of age, average life span is 172.5 days
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nervous system
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• activation of microglia accompanies glycoconjugate storage
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• glycoconjugate storage is seen in the many areas of the brain but not in the cerebral cortex or most other cerebral structures
• substantial glycoconjugate storage is seen in the hindbrain and ventral spinal cord by one year of age
• glycoconjugate storage is increased following doxycycline treatment
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• decrease in the density of interneurons in the ventral horn
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behavior/neurological
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• when given doxycycline starting at 5 weeks of age, a dramatic decrease in motor performance is seen starting at 20 weeks of age
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• progressive tremor develops after 6 months of age
• tremors are milder than in mutant mice not expressing the transgene
• develop progressive tremor from 17-19 weeks of age when given doxycycline starting at 5 weeks of age
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• hindlimbs appear uncoordinated when walking
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• seen when mice are at their humane endpoint, when given doxycycline starting at 5 weeks of age
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muscle
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• progressive limb hypertonia after 6 months of age
• by 1 year of age limb hypertonicity restricts movement
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growth/size/body
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• when given doxycycline starting at 5 weeks of age, weight plateaus at 20 weeks of age and then starts to decrease
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hematopoietic system
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• activation of microglia accompanies glycoconjugate storage
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immune system
|
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• activation of microglia accompanies glycoconjugate storage
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hexbtm1Rlp mutation
(1 available);
any
Hexb mutation
(91 available)
Tg(SYN1-tTA2S,tetO-Hexb)#Tjsa mutation
(0 available)
|
|
|
Doxycycline treatment of Hexbtm1Rlp/Hexbtm1Rlp Tg(Hexb-tTA2S,tetO-Hexb)#Tjsa/0 and Hexbtm1Rlp/Hexbtm1Rlp Tg(SYN1-tTA2S,tetO-Hexb)#Tjsa/0 mice induces storage of glycolipids
mortality/aging
|
|
• at 6 months of age mice do not show overt signs of disease but deteriorate rapidly after this
• average life span of 373 to 404 days
• when given doxycycline starting at 5 weeks of age, average life span is 175 days
|
nervous system
|
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• activation of microglia accompanies glycoconjugate storage
|
|
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• glycoconjugate storage is seen in the many areas of the brain but not in the cerebral cortex or most other cerebral structures
• substantial glycoconjugate storage is seen in the hindbrain and ventral spinal cord by one year of age
• glycoconjugate storage is increased following doxycycline treatment
|
behavior/neurological
|
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• when given doxycycline starting at 5 weeks of age, a dramatic decrease in motor performance is seen starting at 20 weeks of age
|
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• progressive tremor develops after 6 months of age
• tremors are milder than in mutant mice not expressing the transgene
• develop progressive tremor from 17-19 weeks of age when given doxycycline starting at 5 weeks of age
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• hindlimbs appear uncoordinated when walking
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• seen when mice are at their humane endpoint, when given doxycycline starting at 5 weeks of age
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muscle
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• progressive limb hypertonia after 6 months of age
• by 1 year of age limb hypertonicity restricts movement
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growth/size/body
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• when given doxycycline starting at 5 weeks of age, weight plateaus at 20 weeks of age and then starts to decrease
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hematopoietic system
|
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• activation of microglia accompanies glycoconjugate storage
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immune system
|
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• activation of microglia accompanies glycoconjugate storage
|
Analysis Tools
