Phenotypes associated with this allele

• Allele Symbol: Ercc2^tm3Jhjh
• Allele Name: targeted mutation 3, Jan H J Hoeijmakers
• Allele ID: MGI:3664604
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ercc2^tm3Jhjh/Ercc2^tm3Jhjh	involves: 129 * C57BL/6J	MGI:5312312
hm2	Ercc2^tm3Jhjh/Ercc2^tm3Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:3696353
hm3	Ercc2^tm3Jhjh/Ercc2^tm3Jhjh	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3696354
ht4	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm3Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:3696355
cx5	Ercc2^tm3Jhjh/Ercc2^tm3Jhjh Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3696369

Genotype
MGI:5312312

hm1

• Allelic Composition: Ercc2^tm3Jhjh/Ercc2^tm3Jhjh
• Genetic Background: involves: 129 * C57BL/6J

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

Microglia activation in the white matter in Ercc2, Ercc6, and Ercc8 mutants

nervous system

microgliosis ( J:179808 )

• in the white matter

astrocytosis ( J:179808 )

• in the white matter

immune system

microgliosis ( J:179808 )

• in the white matter

hematopoietic system

microgliosis ( J:179808 )

• in the white matter

Genotype
MGI:3696353

hm2

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

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:116054 )

• MEFs are hypersensitve to UV irradiation

Genotype
MGI:3696354

hm3

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

mortality/aging

premature death ( J:112689 )

• mean life span is 546 days compared to 641 days in wild-type mice

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:112689 )

• MEFs are hypersensitve to UV irradiation

abnormal DNA repair ( J:112689 )

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

growth/size/body

cachexia ( J:112689 )

• seen in females from 12 months onward and in most males (3 of 4) surviving to 20 months of age

postnatal growth retardation ( J:112689 )

• small but significant developmental delay is seen in females between P5 and about 2 to 4 weeks of age and in males between P5 and about 2 months of age

neoplasm

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

• within 17 weeks after the start of UV-B exposure (100 J/m²/day) skin and/or eye tumors are seen in 10 of 10 mice but not in any Xpa^tm1Hvs homozygotes or in any wild-type mice

decreased tumor latency ( J:112689 )

• earlier onset of spontaneous tumors

vision/eye

cornea opacity ( J:112689 )

• develops after low level UV-B exposure (100 J/m²/day) in 4 of 10 mice at 10 weeks and 10 of 10 mice at 11 weeks after start of exposure

behavior/neurological

decreased exploration in new environment ( J:112689 )

• males are significantly less active within the first minute of an open field test

limb grasping ( J:112689 )

• spastic and uncoordinated movement of hindlimbs is seen in some males, but not in females, at between P5 and 2 months of age during tail suspension tests

• however, in mice up to 7 months of age neuromotor coordination, gait, and learning capacity are all similar to wild-type mice

reproductive system

reproductive system phenotype ( J:112689 )

N • mice are fertile at least through 6 months of age

abnormal testis morphology ( J:112689 )

♂ • progressive loss of germinal epithelium

nervous system

nervous system phenotype ( J:112689 )

N • no signs of Purkinje cell loss in the cerebellum in mice up to 19 months of age

hematopoietic system

hematopoietic system phenotype ( J:112689 )

N • mice are not anemic

endocrine/exocrine glands

abnormal testis morphology ( J:112689 )

♂ • progressive loss of germinal epithelium

homeostasis/metabolism

abnormal DNA repair ( J:112689 )

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

integument

integument phenotype ( J:112689 )

N • mice do not display brittle hair or ichthyotic skin

acanthosis ( J:112689 )

• seen within 1 week after start of exposure to 200 J/m²/day of UV-B

reddish skin ( J:112689 )

• with exposure to 200 J/m²/day of UV-B for 4 days mice develop erythema within 5 days after the start of exposure

• with exposure to 100 J/m²/day of UV-B for 4 days mice develop erythema by 7 weeks after the start of exposure, unlike Xpa^tm1Hvs homozygotes

skin photosensitivity ( J:112689 )

• with exposure to 200 J/m²/day of UV-B for 4 days mice develop erythema within 5 days and pronounced epidermal hyperplasia with acanthosis and hyperemia within 1 week after the start of exposure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
xeroderma pigmentosum group D		DOID:0110845	OMIM:278730	J:112689

Genotype
MGI:3696355

ht4

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^tm3Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

integument

integument phenotype ( J:116054 )

N • normal hair morphology

Genotype
MGI:3696369

cx5

• 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