Mouse Genome Informatics
hm1
    Ercc2tm2(ERCC2)Jhjh/Ercc2tm2(ERCC2)Jhjh
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular

immune system
N
• somatic hypermutation rates in memory B cells are normal (J:47993)


Mouse Genome Informatics
hm2
    Ercc2tm2(ERCC2)Jhjh/Ercc2tm2(ERCC2)Jhjh
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cutaneous phenotypes of Ercc2tm2(ERCC2)Jhjh/Ercc2tm2(ERCC2)Jhjh and Ercc2tm2(ERCC2)Jhjh/Ercc2tm2Jmch mice

mortality/aging
• most dead by 1 year (J:48256)
• acquire an aged appearance beginning at 3 months of age

tumorigenesis
N
• no sign of cancer predisposition after exposure to a daily dose of 80 J/m2 UV (J:112689)
• increased UV- and DMBA-induced skin cancer susceptibility

pigmentation
• show patchy depigmentation earlier and more frequently than wild-type as they age

behavior/neurological
• occasional tremors, however no overt myelination defect

growth/size/body
• progressive weight loss and cachexia as death neared (J:48256)
• cachectic dwarfism
• evident from birth (J:48256)

hematopoietic system
• mild normochrome anemia at 6 months of age (J:76608)
• progressive with age

immune system
• progressive with age

reproductive system
• older females (~16 months) showed ovarian dysfunction, ranging from complete anovulation to sporadic, seemingly normal, ovulation (J:76608)
(J:48256)
• females lose fertility over time, never produce more than one litter and never produce a litter after 6 months of age, although initial sexual development is unimpaired (J:76608)

skeleton
• showed signs of skeleton abnormalities
• prominently exhibited in older mice (14 months of age) (J:76608)
• reduced radiodensity of skeleton, except for skull, observed in older mice (14 months of age)

adipose tissue
• adipose tissue hypoplasia, most prominent at older age

endocrine/exocrine glands
• benign hyperplasia of the sebaceous gland

homeostasis/metabolism
• decrease in serum levels of branched-chain amino acids (valine, leucine, and isoleucine) at 6 months of age, indicating starvation

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

integument
• benign hyperplasia of the sebaceous gland
• reduced cysteine content of hair and increased fraction of intermedaite filament keratins in hair
• show patchy depigmentation earlier and more frequently than wild-type as they age
• progressive hair loss, beginning at head around P19
• by 4 weeks of age, most hair absent, except a small band of fur at feet and tail
• mew coat grew with second cycle of hair growth, but progressive hair loss again followed
• abnormal cuticle structure
• follicular plugging and dilation
• thickening of the granular layer (J:48256)
• ichthyosis, particularly in the neck region
• ichthyosis, particulary in the neck region

Mouse Models of Human Disease
OMIM IDRef(s)
Trichothiodystrophy, Photosensitive; TTDP 601675 J:48256 , J:76608


Mouse Genome Informatics
ht3
    Ercc2tm1Jhjh/Ercc2tm2(ERCC2)Jhjh
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most dead by 1 year

tumorigenesis
• increased DMBA-induced skin cancer susceptibility
• increased UV- and DMBA-induced skin cancer susceptibility
• increased UV-induced skin cancer susceptibility

adipose tissue
• adipose tissue hypoplasia

behavior/neurological

growth/size/body
• adipose tissue hypoplasia
• progressive weight loss and cachexia as death neared
• evident from birth

hematopoietic system
• decreased RBC count
• decreased hemoglobin concentration

cellular
• increased sensitivity of MEFs to UV irradiation

homeostasis/metabolism
• increased DMBA-induced skin cancer susceptibility

integument
• progressive hair loss, beginning at head ~P19
• by 4 weeks of age, most hair absent, except a small band of fur at feet and tail
• new coat grew with second cycle of hair growth, but progressive hair loss again followed
• abnormal cuticle structure
• follicular plugging and dilation
• ichthyosis, particularly in the neck region
• increased UV- and DMBA-induced skin cancer susceptibility
• ichthyosis, particularly in the neck region

Mouse Models of Human Disease
OMIM IDRef(s)
Trichothiodystrophy, Photosensitive; TTDP 601675 J:48256


Mouse Genome Informatics
ht4
    Ercc2tm1Jmch/Ercc2tm2(ERCC2)Jhjh
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• normal lifespan unlike Ercc2tm2(ERCC2)Jhjh homozygotes (J:116054)

cellular
• UV sensitivity is less than in Ercc2tm2(ERCC2)Jhjh Ercc2tm1Jhjh compound heterozygotes
• decrease in UV sensitivity is not as large as in Ercc2tm2(ERCC2)Jhjh Ercc2tm2Jmch compound heterozygotes

growth/size/body
N
• full rescue of age-related cachexia that is seen in Ercc2tm2(ERCC2)Jhjh homozygotes (J:116054)

integument
• only seen during the first hair cycle and only locally on the back


Mouse Genome Informatics
ht5
    Ercc2tm2(ERCC2)Jhjh/Ercc2tm2Jmch
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cutaneous phenotypes of Ercc2tm2(ERCC2)Jhjh/Ercc2tm2(ERCC2)Jhjh and Ercc2tm2(ERCC2)Jhjh/Ercc2tm2Jmch mice

mortality/aging
N
• normal lifespan unlike Ercc2tm2(ERCC2)Jhjh homozygotes (J:116054)

growth/size/body
N
• full rescue of age-related cachexia that is seen in Ercc2tm2(ERCC2)Jhjh homozygotes (J:116054)
• partial rescue of developmental delay compared to Ercc2tm2(ERCC2)Jhjh homozygotes

hematopoietic system
• partially rescued compared to Ercc2tm2(ERCC2)Jhjh homozygotes

skeleton
N
• mice do not develop osteoporosis or kyphosis any earlier than wild-type mice (J:116054)

cellular
• UV sensitivity is less than in Ercc2tm2(ERCC2)Jhjh homozygotes

integument
N
• absence of acanthosis, hyperkeratosis, and granular layer and sebacious gland hyperplasia (J:116054)
• only seen during the first hair cycle and only locally on the back
• less severe than in Ercc2tm2(ERCC2)Jhjh homozygotes
• only a very low frequency of broken hairs


Mouse Genome Informatics
ht6
    Ercc2tm2(ERCC2)Jhjh/Ercc2tm3Jhjh
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
N
• normal hair morphology (J:116054)


Mouse Genome Informatics
cx7
    Ercc2tm2(ERCC2)Jhjh/Ercc2tm2(ERCC2)Jhjh
Xpatm1Hvs/Xpatm1Hvs

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• incomplete penetrance
• surviving mice dead by 22 days of age

behavior/neurological

growth/size/body
• develop extreme cachexia by 2-3 weeks of age
• exhibit a retarded but steady growth until 1.5 weeks, but fail to gain weight after 2-3 weeks

skeleton

adipose tissue
• complete absence of body fat, including subcutaneous fat

cellular

integument
• severe dilation of hair follicles
• excessive epidermal hyperkeratosis


Mouse Genome Informatics
cx8
    Ercc2tm2(ERCC2)Jhjh/Ercc2tm2(ERCC2)Jhjh
Ercc3tm2Jhjh/Ercc3tm2Jhjh

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 2 days of birth

cellular
• mouse embryonic fibroblasts exhibit increased sensitivity to oxidative stress induced by paraquat treatment compared to similarly treated wild-type cells
• mouse embryonic fibroblasts exhibit slightly increased UV sensitivity compared to cells homozygous for either allele

growth/size/body
• mice fail to grow after birth despite nursing normally