Phenotypes associated with this allele

• Allele Symbol: Ercc1^tm1Dwm
• Allele Name: targeted mutation 1, David W Melton
• Allele ID: MGI:2158940
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ercc1^tm1Dwm/Ercc1^tm1Dwm	involves: 129P2/OlaHsd * BALB/c	MGI:3617383
ht2	Ercc1^tm1Dwm/Ercc1^+	involves: 129P2/OlaHsd * BALB/c	MGI:3617389
cn3	Ercc1^tm1Dwm/Ercc1^tm2Dwm Hr^hr/Hr^hr Tg(KRT5-cre)5132Jlj/0	involves: 129P2/OlaHsd * C57BL/6J * DBA/2J * MF1	MGI:3696991
cx4	Ercc1^tm1Dwm/Ercc1^tm1Dwm Tg(Ttr-Ercc1)17Dwm/0	involves: 129P2/OlaHsd * BALB/c	MGI:3618687

Genotype
MGI:3617383

hm1

• Allelic Composition: Ercc1^tm1Dwm/Ercc1^tm1Dwm
• Genetic Background: involves: 129P2/OlaHsd * BALB/c

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

mortality/aging

postnatal lethality, complete penetrance ( J:15422 )

• died before weaning of liver failure

liver/biliary system

liver degeneration ( J:15422 )

• evidenced by a 15-fold increase in alanine aminotransferase activity

decreased liver function ( J:15422 )

• evidenced by a 2-fold increase in alkaline phosphatase levels and 7-fold increase in bilirubin

cellular

abnormal cell nucleus morphology ( J:15422 )

• liver cells showed variation in nuclear size

aneuploidy ( J:15422 )

• severe aneuploidy seen in liver cells by 3 weeks of age

polyploidy ( J:15422 )

• perinatal liver cells showed varying degrees of polyploidy

growth/size/body

decreased birth body size ( J:15422 )

• runted at birth

Genotype
MGI:3617389

ht2

• Allelic Composition: Ercc1^tm1Dwm/Ercc1⁺
• Genetic Background: involves: 129P2/OlaHsd * BALB/c

liver/biliary system

abnormal liver physiology ( J:15422 )

decreased liver function ( J:15422 )

• an increase in alanine aminotransferase activity approaching values for homozygotes suggested liver cell injury occurs before detectable in histological preparations

Genotype
MGI:3696991

cn3

• Allelic Composition: Ercc1^tm1Dwm/Ercc1^tm2Dwm; Hr^hr/Hr^hr; Tg(KRT5-cre)5132Jlj/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * DBA/2J * MF1

mortality/aging

postnatal lethality, incomplete penetrance ( J:115849 )

• mice with a maternally inherited cre transgene die before weaning

• however, mice with a paternally inherited cre transgene are viable

neoplasm

increased incidence of tumors by UV-induction ( J:115849 )

• mice with a paternally inherited cre transgene develop tumors following chronic exposure to 125 J/m² UVB unlike control mice

• tumors appear earlier and grow faster in mice with a paternally inherited cre transgene compared to control mice receiving a 16-fold higher dose of UVB

• the cumulative UVB EC50 for tumor development is 3.75 kJ/m² in mice with a paternally inherited cre transgene compared to 140 kJ/m²control mice

growth/size/body

decreased birth body size ( J:115849 )

• mice with a maternally inherited cre transgene are severely runted at birth

liver/biliary system

abnormal hepatocyte morphology ( J:115849 )

• mice with a maternally inherited cre transgene develop premature polyploidy in hepatocytes

integument

increased sensitivity to skin irradiation ( J:115849 )

• the minimal erythemal dose of UVB is 40 J/m² in mice with a paternally inherited cre transgene compared to 900 J/m² in controls

• in mice with a paternally inherited cre transgene sensitivity to UVB induced changes in the epidermis (hyperplasia, hypertrophy, hypergranulosis, and hyperkeratosis) are increased

Genotype
MGI:3618687

cx4

• Allelic Composition: Ercc1^tm1Dwm/Ercc1^tm1Dwm; Tg(Ttr-Ercc1)17Dwm/0
• Genetic Background: involves: 129P2/OlaHsd * BALB/c

mortality/aging

premature death ( J:106084 )

• mice survived nolonger than 88 days

reproductive system

abnormal male germ cell apoptosis ( J:80586 )

♂ • spermatagonial cell death is abnormally high in 7 week old mice

absent primary ovarian follicles ( J:80586 )

♀ • no primary follicles are found in the periphery of the ovary

abnormal ovarian folliculogenesis ( J:80586 )

♀ • majority of oocytes appeared to be degenerating

abnormal gametogenesis ( J:80586 )

decreased germ cell number ( J:80586 )

• significantly fewer germs cells in both males and females

abnormal spermatogenesis ( J:80586 )

♂

female infertility ( J:80586 )

♀

male infertility ( J:80586 )

♂

cellular

decreased germ cell number ( J:80586 )

• significantly fewer germs cells in both males and females

abnormal chromosome number ( J:106084 )

• polyploid nuclei found in cells of kidney proximal tubules

polyploidy ( J:106084 )

• process of polyploidy is similar to the premature liver polyploidy of mice homozygous for Ercc1^tm1Dwm

abnormal male germ cell apoptosis ( J:80586 )

♂ • spermatagonial cell death is abnormally high in 7 week old mice

endocrine/exocrine glands

absent primary ovarian follicles ( J:80586 )

♀ • no primary follicles are found in the periphery of the ovary

abnormal ovarian folliculogenesis ( J:80586 )

♀ • majority of oocytes appeared to be degenerating

renal/urinary system

abnormal renal tubule morphology ( J:106084 )

kidney failure ( J:106084 )

• mice died between 61 and 88 days

homeostasis/metabolism

increased circulating lactate level ( J:106084 )

• plasma lactate levels were 40% higher in 7-week-old mice compared to controls