Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6tm1Gvh mutation
(1 available);
any
Ercc6 mutation
(78 available)
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hearing/vestibular/ear
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• reduction in the number of inner hair cells in the base by 16 weeks of age
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• progressive degeneration of outer hair cells following a basal-to-apical gradient, with complete loss of outer hair cells in the basal turn of the organ of Corti in all 13 week old mutants, while the middle and apical regions show normal hair cells at this time, and variable outer hair cell loss in the middle turns by 16 weeks of age
• outer hair cells are more affected than inner hair cells
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• severe degeneration in the base
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• severe degeneration in the base
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• severe degeneration of supporting cells (Deiters cells and pillar cells) in the base, with the basilar membrane fully intact
• middle sections show some signs of supporting cell degeneration at 16 weeks of age, with collapse of Nuels space
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• the ABR thresholds at 16 and 32 kHz are modestly elevated at 6 weeks of age, with a further increase between 6 and 12 weeks and 36 weeks
• by 12 weeks of age, mice have undergone an approximate 57 dB sound pressure level threshold shift compared with controls at 16 and 32 kHz, corresponding to the middle and basal regions of the cochlea
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• DPOAEs at frequencies between 10 and 16 kHz are reduced in amplitude or are absent at 8 and 12 weeks of age, indicating outer hair cell impairment
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• mice show progressive hearing loss starting after 6 weeks of age
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nervous system
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• reduction in the number of inner hair cells in the base by 16 weeks of age
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• progressive degeneration of outer hair cells following a basal-to-apical gradient, with complete loss of outer hair cells in the basal turn of the organ of Corti in all 13 week old mutants, while the middle and apical regions show normal hair cells at this time, and variable outer hair cell loss in the middle turns by 16 weeks of age
• outer hair cells are more affected than inner hair cells
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6tm1Gvh mutation
(1 available);
any
Ercc6 mutation
(78 available)
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Microglia activation in the white matter in Ercc2, Ercc6, and Ercc8 mutants
cellular
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• MEFs display UV sensitivity
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growth/size/body
vision/eye
nervous system
hematopoietic system
immune system
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6tm1Gvh mutation
(1 available);
any
Ercc6 mutation
(78 available)
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hearing/vestibular/ear
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• the ABR thresholds at 16 and 32 kHz progressively increase with age
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• mice show progressive hearing loss starting after 6 weeks of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6tm1Gvh mutation
(1 available);
any
Ercc6 mutation
(78 available)
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growth/size/body
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• small but highly significant reduction in body weights of males at 10 weeks of age that is less pronounced in females
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behavior/neurological
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• at high doses of UV-B light, develop photophobia (mice avoid contact with daylight by keeping their eyes closed) that disappears after a few days of treatment
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• have more difficulties remaining on a rotating cylinder in a Rotarod task
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• have more difficulties remaining on a rotating cylinder in a Rotarod task
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• significantly less active, especially in the first 30 s of an open-field exploratory test, indicating that more time to adapt to a new environment is required
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• some start to develop circling behavior after 6 months of age, however do not develop tremors or limb ataxia
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cellular
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• fibroblasts display UV sensitivity, defective resumption of transcription after UV exposure, and a complete loss of transcription-coupled repair of cyclobutane pyrimidine dimers in the transcribed strand of an active gene
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• fibroblasts display UV sensitivity
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neoplasm
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• increased incidence of skin and eye tumors after exposure to UV irradiation and of skin tumors after DMBA exposure
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homeostasis/metabolism
vision/eye
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• chronic exposure to low doses of UV-B resulted in redness and scaling of skin, pruritus, acanthosis, parakeratosis, corneal opacities, and severe ulceration of the eyes
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• at high doses of UV-B light, develop photophobia (mice avoid contact with daylight by keeping their eyes closed) that disappears after a few days of treatment
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integument
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• develop severe erythema and epidermal hyperplasia after exposure of dorsal skin to UV-B light
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Neurodegenerative changes in Ercc6tm1Gvh/Ercc6tm1Gvh Xpatm1Gvh/Xpatm1Hvs Tg(Pcp2-cre)2Mpin/0 mice
nervous system
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• argyrophilic axonal degeneration in the cerebellar white matter and cerebellar nuclei
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immune system
hematopoietic system
Ercc6tm1Gvh/Ercc6tm1Gvh Xpatm1Gvh/Xpatm1Hvs Tg(CAG-cre)13Miya/0 mice are severely reduced in size
mortality/aging
behavior/neurological
growth/size/body
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6tm1Gvh mutation
(1 available);
any
Ercc6 mutation
(78 available)
Tg(Camk2a-cre)1Szi mutation
(0 available)
Xpatm1Gvh mutation
(0 available);
any
Xpa mutation
(22 available)
Xpatm1Hvs mutation
(4 available);
any
Xpa mutation
(22 available)
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Dilated ventricles and brain atrophy in Ercc6tm1Gvh/Ercc6tm1Gvh Xpatm1Gvh/Xpatm1Hvs Tg(Camk2a-cre)1Szi/0 mice
mortality/aging
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• between 12 and 22 months
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nervous system
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• from 9 to 12 months of age, mice exhibit seizure behavior characterized by episodes of immobility unlike control mice
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• at 6 to 12 months of age, mice exhibit atrophy in the telencephalon (cortex, hippocampus, caudate-putamen and septum) unlike control mice
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• atrophic at 6 to 12 months of age
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• atrophic at 6 to 12 months of age
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• mild atrophy at 6 months of age
• severe atrophy in older mice
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• at 6 to 12 months of age
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behavior/neurological
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• from 9 to 12 months of age, mice exhibit seizure behavior characterized by episodes of immobility unlike control mice
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growth/size/body
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• at 9 to 12 months of age
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• at 9 to 12 months of age
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immune system
hematopoietic system
Skeletal and neurological abnormalities in Ercc6tm1Gvh/Ercc6tm1Gvh Xpatm1Hvs/Xpatm1Hvs mice
mortality/aging
growth/size/body
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• near normal size of skull at P11 and P21, implying that postnatal growth retardation is restricted to the trunk
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cellular
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• retina exhibits enhanced ionizing radiation sensitivity
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adipose tissue
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• substantial loss of abdominal fat is seen in P15 mutants
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• generalized lipodystrophy (loss and abnormal redistribution of body fat)
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behavior/neurological
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• tremors become evident around P10
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• abnormal posture of the hind limbs (flexion rather than extension in tail suspension test) becomes evident around P10
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• disturbed gait from P15 onwards, showing a non-uniform alternating left-right step pattern and unevenly spaced shorter strides
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• unevenly spaced shorter strides
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homeostasis/metabolism
vision/eye
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• retina exhibits enhanced ionizing radiation sensitivity
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• number of apoptotic cells in the inner nuclear layer of the retina is increased compared to wild-type or single mutant mice
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• number of apoptotic cells in the outer nuclear layer of the retina is increased compared to wild-type or single mutant mice
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• increased apoptosis in the outer and inner nuclear layers
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skeleton
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• kyphosis is seen at P21 but not at P11
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• less developed tibiae growth plate
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nervous system
muscle
liver/biliary system
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• pups exhibit enhanced hepatic accumulation of glycogen in unusually large vesicles
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• livers show enhanced accumulation of triglycerides, indicating hepatic steatosis
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limbs/digits/tail
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• as pups lose weight in the third week of life, bone growth proceeds, resulting in relatively large extremities
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mortality/aging
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• number of double mutant pups is about 3-fold below the expected numbers, however normal numbers are seen at E18.5, indicating some lethality during or shortly after birth
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growth/size/body
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• develop progressive cachexia in the third week of life
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homeostasis/metabolism
cellular
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• MEFs are more UV-sensitive
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• analysis of UV-induced repair synthesis and RNA synthesis recovery show complete inactivation of nucleotide excision repair (NER)
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mortality/aging
growth/size/body
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• mutants exhibit whole-body wasting
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• mutants fail to thrive and show a 50% reduction in body weight at death
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behavior/neurological
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• abnormal clasping reflex and complete inactivity upon tail suspension
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• on the rotarod, mutants are unable to stay on the rotating beam
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• mutants exhibit deficits in the catwalk gait analysis test, with shorter stride lengths than controls and reduced base of support in both the front and hind paws
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nervous system
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• mutants exhibit widespread reduction of myelin basic protein (MBP) and myelin in the sensorimotor cortex, the stratum radiatum, the corpus callosum, and the anterior commissure
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• oligodendrocytes appear to exhibit normal proliferation and differentiation, however they are unable to generate sufficient MBP or to maintain the proper myelination during early development, indicating that they may not mature into MBP-synthesizing cells
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• mutants exhibit hypomyelination in the anterior commissure and corpus callosum due to dysmyelination and not demyelination
• reduction in both the number of myelinated axons and the average diameter of myelin surrounding the axons
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ercc6tm1Gvh mutation
(1 available);
any
Ercc6 mutation
(78 available)
Xpatm1Tnka mutation
(0 available);
any
Xpa mutation
(22 available)
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mortality/aging
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• die around 21 days of age
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growth/size/body
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• low body weight and size develop after birth
• 40% weight reduction at 2 weeks of age
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behavior/neurological
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• clasp hind limbs when suspended by the tail
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• starting around 1 week of age
• clearly evident at 2 weeks of age
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• sit with hind limbs spread for balance
• fall down often
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• walk with a wide gait
• "waltzing" locomotion
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nervous system
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• fewer proliferating external granular cells at 8 days
• significantly increased number of apoptotic cells
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• impaired foliation and sulcus formation
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• 20% brain weight reduction at 2 weeks of age
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• dendritic trees are reduced in length
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• becomes strikingly small
• normal at birth
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cellular
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• fewer proliferating external granular cells at 8 days
• significantly increased number of apoptotic cells
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Ercc6tm1Gvh/Ercc6tm1Gvh Xpatm1Hvs/Xpatm1Hvs mice display postnatal growth retardation
mortality/aging
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• number of double mutant pups is about 3-fold below the expected numbers, however normal numbers are seen at E18.5, indicating some lethality during or shortly after birth
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growth/size/body
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• develop progressive cachexia in the third week of life
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homeostasis/metabolism
cellular
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• MEFs are more UV-sensitive than single Xpa mutants
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• analysis of UV-induced repair synthesis and RNA synthesis recovery show complete inactivation of nucleotide excision repair (NER)
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Analysis Tools