Phenotypes associated with this allele

• Allele Symbol: Xpa^tm1Hvs
• Allele Name: targeted mutation 1, Harry van Steeg
• Allele ID: MGI:1857939
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd	MGI:3836473
hm2	Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6	MGI:2386450
hm3	Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6J	MGI:3767956
ht4	Xpa^tm1Gvh/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6J	MGI:5312288
cn5	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Gvh/Xpa^tm1Hvs Tg(Pcp2-cre)2Mpin/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5312301
cn6	Xpa^tm1Gvh/Xpa^tm1Hvs Tg(CAG-cre)13Miya/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:5312289
cn7	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Gvh/Xpa^tm1Hvs Tg(CAG-cre)13Miya/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:5312296
cn8	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Gvh/Xpa^tm1Hvs Tg(Camk2a-cre)1Szi/0	involves: 129P2/OlaHsd * C57BL/6J * CBA	MGI:5312300
cx9	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Hvs/Xpa^tm1Hvs	B6.129P2-Xpa^tm1Hvs Ercc6^tm1Gvh	MGI:3767861
cx10	Trp53^tm1Tyj/Trp53^+ Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:4947935
cx11	Ercc3^tm2Jhjh/Ercc3^tm2Jhjh Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6	MGI:3836474
cx12	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm2(ERCC2)Jhjh Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6	MGI:2386447
cx13	Ercc2^tm3Jhjh/Ercc2^tm3Jhjh Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3696369
cx14	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6J	MGI:3767853

Genotype
MGI:3836473

hm1

• Allelic Composition: Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd

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

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:145759 )

homeostasis/metabolism

skin edema ( J:145759 )

• following UV irradiation

integument

skin edema ( J:145759 )

• following UV irradiation

abnormal epidermal layer morphology ( J:145759 )

• following UV irradiation, mice exhibit recurrent loss of the epidermis unlike similarly treated wild-type mice

acanthosis ( J:145759 )

• following UV irradiation

reddish skin ( J:145759 )

• following UV irradiation

scaly skin ( J:145759 )

• following UV irradiation

Genotype
MGI:2386450

hm2

• Allelic Composition: Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:28710 )

• incomplete penetrance, ~50% dead after E13, with normal ratios seen up to that time

• death likely due to severe anemia

• mice that survive this period are born and survive up to 13 months of age with no obvious abnormalities and no spontaneous tumor development

liver/biliary system

small liver ( J:28710 )

• decreased liver size after E13

growth/size/body

fetal growth retardation ( J:28710 )

• observed after E13

hematopoietic system

anemia ( J:28710 )

• approximately 50% of the embryos died in the mid-fetal period due to severe anemia

impaired hematopoiesis ( J:28710 )

• disturbed liver hematopoiesis shown after E13

neoplasm

increased incidence of induced tumors ( J:28710 )

• enhanced UV-induced skin and eye tumor and DMBA-induced skin tumor susceptibility

increased incidence of tumors by UV-induction ( J:112689 )

• at 23 weeks after the start of UV-B exposure (100 J/m²/day) skin and/or eye tumors are seen in 1 of 5 mice and by 31 weeks all 5 mice have tumors, while no tumors are seen in wild-type mice

cellular

abnormal cell physiology ( J:112689 )

• following UV exposure DNA incision activity and unscheduled DNA synthesis are decreased compared to wild-type MEFs

vision/eye

corneal opacity ( J:112689 )

• develops after low level UV-B exposure (100 J/m²/day) in 3 of 5 mice at 11 weeks after start of exposure

integument

pallor ( J:28710 )

• light appearance of the embryo in its intact yolk sac after E13

Genotype
MGI:3767956

hm3

• Allelic Composition: Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:122013 )

• MEFs display high UV sensitivity

Genotype
MGI:5312288

ht4

• Allelic Composition: Xpa^tm1Gvh/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:179808 )

• mouse embryonic fibroblasts are resistant to UV irradiation compared with control mice

Genotype
MGI:5312301

cn5

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpa^tm1Gvh/Xpa^tm1Hvs; Tg(Pcp2-cre)2Mpin/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

Neurodegenerative changes in Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Gvh/Xpa^tm1Hvs Tg(Pcp2-cre)2Mpin/0 mice

nervous system

microgliosis ( J:179808 )

Purkinje cell degeneration ( J:179808 )

astrocytosis ( J:179808 )

axon degeneration ( J:179808 )

• argyrophilic axonal degeneration in the cerebellar white matter and cerebellar nuclei

immune system

microgliosis ( J:179808 )

hematopoietic system

microgliosis ( J:179808 )

Genotype
MGI:5312289

cn6

• Allelic Composition: Xpa^tm1Gvh/Xpa^tm1Hvs; Tg(CAG-cre)13Miya/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:179808 )

• in mouse embryonic fibroblasts

Genotype
MGI:5312296

cn7

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpa^tm1Gvh/Xpa^tm1Hvs; Tg(CAG-cre)13Miya/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Gvh/Xpa^tm1Hvs Tg(CAG-cre)13Miya/0 mice are severely reduced in size

mortality/aging

postnatal lethality, complete penetrance ( J:179808 )

behavior/neurological

abnormal gait ( J:179808 )

growth/size/body

cachexia ( J:179808 )

postnatal growth retardation ( J:179808 )

Genotype
MGI:5312300

cn8

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpa^tm1Gvh/Xpa^tm1Hvs; Tg(Camk2a-cre)1Szi/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * CBA

Dilated ventricles and brain atrophy in Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Gvh/Xpa^tm1Hvs Tg(Camk2a-cre)1Szi/0 mice

mortality/aging

premature death ( J:179808 )

• between 12 and 22 months

nervous system

seizures ( J:179808 )

• from 9 to 12 months of age, mice exhibit seizure behavior characterized by episodes of immobility unlike control mice

microgliosis ( J:179808 )

abnormal telencephalon morphology ( J:179808 )

• at 6 to 12 months of age, mice exhibit atrophy in the telencephalon (cortex, hippocampus, caudate-putamen and septum) unlike control mice

dilated lateral ventricle ( J:179808 )

• at 65 weeks

abnormal dorsal striatum morphology ( J:179808 )

• atrophic at 6 to 12 months of age

hippocampus atrophy ( J:179808 )

• atrophic at 6 to 12 months of age

abnormal cerebral cortex morphology ( J:179808 )

• mild atrophy at 6 months of age

• severe atrophy in older mice

abnormal neocortex morphology ( J:179808 )

• atrophic at 65 weeks

thin cerebral cortex ( J:179808 )

• at 6 to 12 months of age

astrocytosis ( J:179808 )

neuron degeneration ( J:179808 )

behavior/neurological

increased thigmotaxis ( J:179808 )

impaired coordination ( J:179808 )

• at 12 months of age

seizures ( J:179808 )

• from 9 to 12 months of age, mice exhibit seizure behavior characterized by episodes of immobility unlike control mice

growth/size/body

decreased body size ( J:179808 )

• at 9 to 12 months of age

decreased body weight ( J:179808 )

• at 9 to 12 months of age

immune system

microgliosis ( J:179808 )

hematopoietic system

microgliosis ( J:179808 )

Genotype
MGI:3767861

cx9

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: B6.129P2-Xpa^tm1Hvs Ercc6^tm1Gvh

Skeletal and neurological abnormalities in Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Hvs/Xpa^tm1Hvs mice

mortality/aging

premature aging ( J:122013 )

growth/size/body

postnatal growth retardation ( J:122013 )

• near normal size of skull at P11 and P21, implying that postnatal growth retardation is restricted to the trunk

cellular

increased cellular sensitivity to gamma-irradiation ( J:122013 )

• retina exhibits enhanced ionizing radiation sensitivity

adipose tissue

abnormal abdominal fat pad morphology ( J:122013 )

• substantial loss of abdominal fat is seen in P15 mutants

lipodystrophy ( J:122013 )

• generalized lipodystrophy (loss and abnormal redistribution of body fat)

behavior/neurological

dystonia ( J:122013 )

tremors ( J:122013 )

• tremors become evident around P10

ataxia ( J:122013 )

abnormal limb posture ( J:122013 )

• abnormal posture of the hind limbs (flexion rather than extension in tail suspension test) becomes evident around P10

abnormal gait ( J:122013 )

• disturbed gait from P15 onwards, showing a non-uniform alternating left-right step pattern and unevenly spaced shorter strides

short stride length ( J:122013 )

• unevenly spaced shorter strides

homeostasis/metabolism

hypoglycemia ( J:122013 )

• significantly lower blood glucose levels; following an initial reduction of about 30% in 7 and 10 day old mutants, blood glucose levels start to drop at P15

• presence of milk and food in the stomach and normal appearance of intestinal epithelium indicates that hypoglycemia is not due to food intake

increased liver glycogen level ( J:122013 )

• pups exhibit enhanced hepatic accumulation of glycogen in unusually large vesicles

vision/eye

abnormal retina morphology ( J:122013 )

• retina exhibits enhanced ionizing radiation sensitivity

abnormal retina inner nuclear layer morphology ( J:122013 )

• number of apoptotic cells in the inner nuclear layer of the retina is increased compared to wild-type or single mutant mice

abnormal retina outer nuclear layer morphology ( J:122013 )

• number of apoptotic cells in the outer nuclear layer of the retina is increased compared to wild-type or single mutant mice

retina degeneration ( J:122013 )

• increased apoptosis in the outer and inner nuclear layers

skeleton

kyphosis ( J:122013 )

• kyphosis is seen at P21 but not at P11

abnormal epiphyseal plate morphology ( J:122013 )

• less developed tibiae growth plate

nervous system

abnormal Purkinje cell morphology ( J:122013 )

• Purkinje cell loss

muscle

dystonia ( J:122013 )

liver/biliary system

increased liver glycogen level ( J:122013 )

• pups exhibit enhanced hepatic accumulation of glycogen in unusually large vesicles

hepatic steatosis ( J:122013 )

• livers show enhanced accumulation of triglycerides, indicating hepatic steatosis

limbs/digits/tail

long limbs ( J:122013 )

• as pups lose weight in the third week of life, bone growth proceeds, resulting in relatively large extremities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cockayne syndrome		DOID:2962		J:122013

Genotype
MGI:4947935

cx10

• Allelic Composition: Trp53^tm1Tyj/Trp53⁺; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

neoplasm

increased incidence of tumors by chemical induction ( J:170769 )

• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors

increased urinary system tumor incidence ( J:170769 )

• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:170769 )

• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors

renal/urinary system

increased urinary system tumor incidence ( J:170769 )

• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors

Genotype
MGI:3836474

cx11

• Allelic Composition: Ercc3^tm2Jhjh/Ercc3^tm2Jhjh; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:145759 )

• most severely affected mice die between 3 and 4 weeks of age

premature aging ( J:145759 )

• some mice exhibit symptoms of premature aging including progressive cachexia, early cessation of growth, neurological abnormalities, and severely reduced life span

• however, mice do not exhibit osteoporosis or increased incidence of spontaneous tumors

reproductive system

testicular atrophy ( J:145759 )

♂ • prematurely at 1.5 years of age

behavior/neurological

tremors ( J:145759 )

• occasional in 30% of mice at 2 months of age

ataxia ( J:145759 )

• occasional in 30% of mice at 2 months of age

impaired balance ( J:145759 )

• in the last week of live for mice that die prematurely

impaired limb coordination ( J:145759 )

• at 2 months of age, impaired hindlimb coordination is occasional observed in 30% of mice unlike in wild-type mice

abnormal gait ( J:145759 )

• mild gait abnormalities are observed in mice from P12 to 2 months of age and again in ageing mice that develop pronounced kyphosis

hyperactivity ( J:145759 )

• 5 of 23 mice exhibit abnormal hyperactivity, excitability and nervous behavior but only 1 mouse continued to display these behaviors beyond 2 months of age

cellular

increased cellular sensitivity to gamma-irradiation ( J:145759 )

increased cellular sensitivity to oxidative stress ( J:145759 )

• mouse embryonic fibroblasts exhibit increased sensitivity to oxidative stress induced by paraquat treatment compared to similarly treated wild-type cells

increased cellular sensitivity to ultraviolet irradiation ( J:145759 )

growth/size/body

decreased body weight ( J:145759 )

• some mice exhibit reduced weight between P10 and P21 compared to wild-type mice

slow postnatal weight gain ( J:145759 )

• after P10 mice fail to gain weight

• however, mice surviving after 3 months reach normal weight

cachexia ( J:145759 )

skeleton

abnormal cranium morphology ( J:145759 )

• at 1.5 years of age, mice exhibit deformed and thickened skulls, mainly in the occipital region, compared to wild-type mice

kyphosis ( J:145759 )

• severe in the last week of live for mice that die prematurely

• between 8 and 12 months, 5 of 23 mice exhibit premature kyphosis

muscle

muscle hypertonia ( J:145759 )

• occasional in 30% of mice at 2 months of age

craniofacial

abnormal cranium morphology ( J:145759 )

• at 1.5 years of age, mice exhibit deformed and thickened skulls, mainly in the occipital region, compared to wild-type mice

endocrine/exocrine glands

testicular atrophy ( J:145759 )

♂ • prematurely at 1.5 years of age

Genotype
MGI:2386447

cx12

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh}; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:76608 )

• incomplete penetrance

postnatal lethality, complete penetrance ( J:76608 )

• surviving mice dead by 22 days of age

premature aging ( J:76608 )

behavior/neurological

abnormal gait ( J:76608 )

growth/size/body

cachexia ( J:76608 )

• develop extreme cachexia by 2-3 weeks of age

postnatal growth retardation ( J:76608 )

• exhibit a retarded but steady growth until 1.5 weeks, but fail to gain weight after 2-3 weeks

skeleton

kyphosis ( J:76608 )

osteoporosis ( J:76608 )

adipose tissue

abnormal adipose tissue distribution ( J:76608 )

• complete absence of body fat, including subcutaneous fat

cellular

abnormal cell death ( J:76608 )

increased cellular sensitivity to X-ray irradiation ( J:76608 )

• seen in MEFs

increased cellular sensitivity to oxidative stress ( J:76608 )

increased cellular sensitivity to ultraviolet irradiation ( J:76608 )

integument

dilated hair follicle ( J:76608 )

• severe dilation of hair follicles

hyperkeratosis ( J:76608 )

• excessive epidermal hyperkeratosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
photosensitive trichothiodystrophy		DOID:2960		J:76608
xeroderma pigmentosum group A		DOID:0110843	OMIM:278700	J:76608

Genotype
MGI:3696369

cx13

• Allelic Composition: Ercc2^tm3Jhjh/Ercc2^tm3Jhjh; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

mortality/aging

postnatal lethality, complete penetrance ( J:112689 )

• maximal life span of about 3 weeks

behavior/neurological

tremors ( J:112689 )

• tremors and spasticity

ataxia ( J:112689 )

impaired balance ( J:112689 )

• progressive disturbance in balance

growth/size/body

postnatal growth retardation ( J:112689 )

• growth failure despite no obvious impairment in nursing

nervous system

Purkinje cell degeneration ( J:112689 )

• at 20 days of age Purkinje cell degeneration with loss of both proximal and distal dendrites and cell bodies is seen

• reduction in cell numbers to 69% and 31% of wild-type in the vermis and hemispheres, respectively

Genotype
MGI:3767853

cx14

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Hvs/Xpa^tm1Hvs mice display postnatal growth retardation

mortality/aging

perinatal lethality, incomplete penetrance ( J:122013 )

• 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

postnatal lethality, complete penetrance ( J:122013 )

• die before P22

growth/size/body

cachexia ( J:122013 )

• develop progressive cachexia in the third week of life

disproportionate dwarf ( J:122013 )

postnatal growth retardation ( J:122013 )

homeostasis/metabolism

abnormal base-excision repair ( J:122013 )

• analysis of UV-induced repair synthesis and RNA synthesis recovery show complete inactivation of nucleotide excision repair (NER)

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:122013 )

• MEFs are more UV-sensitive than single Xpa mutants

abnormal base-excision repair ( J:122013 )

• analysis of UV-induced repair synthesis and RNA synthesis recovery show complete inactivation of nucleotide excision repair (NER)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cockayne syndrome		DOID:2962		J:122013