Phenotypes associated with this allele

• Allele Symbol: Ercc1^tm1Jhjh
• Allele Name: targeted mutation 1, Jan H J Hoeijmakers
• Allele ID: MGI:2183944
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ercc1^tm1Jhjh/Ercc1^tm1Jhjh	either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * FVB)	MGI:3055851
hm2	Ercc1^tm1Jhjh/Ercc1^tm1Jhjh	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3804449
hm3	Ercc1^tm1Jhjh/Ercc1^tm1Jhjh	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5553271
hm4	Ercc1^tm1Jhjh/Ercc1^tm1Jhjh	involves: C57BL/6 * FVB/N	MGI:3055853
ht5	Ercc1^tm1Jhjh/Ercc1^tm2Jhjh	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5553273
ht6	Ercc1^tm1Jhjh/Ercc1^tm2Jhjh	involves: 129P2/OlaHsd * C57BL/6J * FVB/N	MGI:6386114
cn7	Ercc1^tm1Jhjh/Ercc1^tm3Jhjh Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N	MGI:5553270

Genotype
MGI:3055851

hm1

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm1Jhjh
• Genetic Background: either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * FVB)

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

mortality/aging

premature death ( J:41161 )

• mutants do not live beyond 38 days of age

embryonic lethality during organogenesis, incomplete penetrance ( J:41161 )

• many mutant embryos die by E13.5

growth/size/body

embryonic growth retardation ( J:41161 )

• on a mixed 129P2/OlaHsd and C57BL/6 background embryonic growth delay is seen

decreased body size ( J:41161 )

• homozygotes are severely runted

embryo

embryonic growth retardation ( J:41161 )

• on a mixed 129P2/OlaHsd and C57BL/6 background embryonic growth delay is seen

Genotype
MGI:3804449

hm2

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm1Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

mortality/aging

postnatal lethality, incomplete penetrance ( J:117488 )

• most die by four weeks after birth

premature aging ( J:117488 )

growth/size/body

embryonic growth retardation ( J:117488 )

• mildly retarded

abnormal postnatal growth ( J:117488 )

• growth arrests in the second week of life

postnatal growth retardation ( J:117488 )

• mildly retarded

fetal growth retardation ( J:117488 )

• mildly retarded

embryo

embryonic growth retardation ( J:117488 )

• mildly retarded

cellular

increased cellular sensitivity to oxidative stress ( J:117488 )

• mutant ES cells and MEFs are mildly, but significantly, hypersensitive to oxidative damage compared to wild-type

increased hepatocyte apoptosis ( J:117488 )

• apoptotic cells are increased in mutant liver compared to age-matched controls

decreased cell proliferation ( J:117488 )

• cellular proliferation is decreased compared to age matched controls

decreased hepatocyte proliferation ( J:117488 )

• senescent, polyploid hepatocytes are prominent in mutants but not age-matched controls

early cellular replicative senescence ( J:117488 )

• MEFS exhibit premature replicative senescence

abnormal DNA repair ( J:117488 )

behavior/neurological

dystonia ( J:117488 )

ataxia ( J:117488 )

• progressive ataxia

homeostasis/metabolism

abnormal DNA repair ( J:117488 )

decreased circulating glucose level ( J:117488 )

decreased circulating insulin level ( J:117488 )

decreased circulating insulin-like growth factor I level ( J:117488 )

increased liver triglyceride level ( J:117488 )

• triglyceride accumulation is observed in the liver in young mutants as is seen in older controls

acidosis ( J:117488 )

increased urine protein level ( J:117488 )

liver/biliary system

increased hepatocyte apoptosis ( J:117488 )

• apoptotic cells are increased in mutant liver compared to age-matched controls

decreased hepatocyte proliferation ( J:117488 )

• senescent, polyploid hepatocytes are prominent in mutants but not age-matched controls

increased liver triglyceride level ( J:117488 )

• triglyceride accumulation is observed in the liver in young mutants as is seen in older controls

hepatic steatosis ( J:117488 )

• progressive steatosis

muscle

dystonia ( J:117488 )

decreased skeletal muscle mass ( J:117488 )

• sarcopenia

renal/urinary system

increased urine protein level ( J:117488 )

abnormal kidney physiology ( J:117488 )

• renal insufficiency

skeleton

kyphosis ( J:117488 )

decreased bone mineral density ( J:117488 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
XFE progeroid syndrome		DOID:0060590	OMIM:610965	J:117488

Genotype
MGI:5553271

hm3

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm1Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

premature death ( J:206925 )

• mice die between 3 and 4 weeks of age

hematopoietic system

decreased common myeloid progenitor cell number ( J:206925 )

• at 3 weeks

decreased granulocyte monocyte progenitor cell number ( J:206925 )

• decreased colony forming unit-granulocyte (CFU-G) and granulocyte-macrophage (CFU-GM) at 3 weeks

decreased erythroid progenitor cell number ( J:206925 )

• CFU-B at 3 weeks

decreased hematopoietic stem cell number ( J:206925 )

• decreased total LSK+ cells at 3 weeks

decreased megakaryocyte-erythroid progenitor cell number ( J:206925 )

• at 3 weeks

liver/biliary system

abnormal hepatocyte morphology ( J:206925 )

• cells with enlarged nuclei in the liver

growth/size/body

decreased body size ( J:206925 )

decreased body weight ( J:206925 )

• at 3 weeks

Genotype
MGI:3055853

hm4

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm1Jhjh
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

lethality at weaning, complete penetrance ( J:92471 )

• mutants die around 3 weeks of age from liver failure

hematopoietic system

decreased B cell proliferation ( J:92471 )

• B cell proliferation is reduced to 76% wild-type

abnormal class switch recombination ( J:92471 )

• class switching recombination for IgG1, IgG2a, IgG2b, IgG3, and IgA is reduced 20-55%

• the mutation spectra and location are altered in GL Smu segments

spleen hypoplasia ( J:92471 )

• at P19-21 spleen contain 10-fold fewer cells

immune system

decreased B cell proliferation ( J:92471 )

• B cell proliferation is reduced to 76% wild-type

abnormal class switch recombination ( J:92471 )

• class switching recombination for IgG1, IgG2a, IgG2b, IgG3, and IgA is reduced 20-55%

• the mutation spectra and location are altered in GL Smu segments

spleen hypoplasia ( J:92471 )

• at P19-21 spleen contain 10-fold fewer cells

liver/biliary system

abnormal liver physiology ( J:92471 )

• liver failure is seen

cellular

decreased B cell proliferation ( J:92471 )

• B cell proliferation is reduced to 76% wild-type

Genotype
MGI:5553273

ht5

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm2Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

hematopoietic system

decreased common myeloid progenitor cell number ( J:206925 )

• at 3, 10 and 20 weeks

• decreased colony forming unit-granulocyte (CFU-G) and granulocyte-macrophage (CFU-GM) at 3, 10 and 20 weeks

decreased granulocyte monocyte progenitor cell number ( J:206925 )

• at 10 and 20 weeks

decreased erythroid progenitor cell number ( J:206925 )

• CFU-B at 3 weeks

decreased hematopoietic stem cell number ( J:206925 )

• decreased total LSK+ cells with a 3-fold decrease in the fraction of multipotent progenitors (MPP) but an increase in the fraction of long term hematopoietic stem cells (HSCs) at 3 weeks; increased fraction of short term HSCs but a decrease in MPP at 10 and 20 weeks

decreased megakaryocyte-erythroid progenitor cell number ( J:206925 )

• at 10 and 20 weeks

liver/biliary system

abnormal hepatocyte morphology ( J:206925 )

• cells with enlarged nuclei in the liver

growth/size/body

decreased body weight ( J:206925 )

• at 3, 10 and 20 weeks of age

Genotype
MGI:6386114

ht6

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm2Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB/N

hearing/vestibular/ear

cochlear hair cell degeneration ( J:280844 )

increased or absent threshold for auditory brainstem response ( J:280844 )

• at 5 weeks of age with further deterioration at 9 weeks at 8 and 16, but not 4, kHz

abnormal distortion product otoacoustic emission ( J:280844 )

• reduced at 12, but not 4, weeks

impaired hearing ( J:280844 )

• progressive

vision/eye

increased retina apoptosis ( J:280844 )

• in the outer nuclear layer at 4, 9, 18 and 25 weeks

thin retina outer nuclear layer ( J:280844 )

• progressive starting at 25 weeks

nervous system

cochlear hair cell degeneration ( J:280844 )

behavior/neurological

abnormal optokinetic reflex ( J:280844 )

• progressive reduction at 10 and 14 weeks

• smaller saccades at all ages

• however, the main sequence is normal

cellular

increased retina apoptosis ( J:280844 )

• in the outer nuclear layer at 4, 9, 18 and 25 weeks

Genotype
MGI:5553270

cn7

• Allelic Composition: Ercc1^tm1Jhjh/Ercc1^tm3Jhjh; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N

hematopoietic system

hematopoietic system phenotype ( J:206925 )

N • mice exhibit normal blood cell parameters and colony-forming progenitors in the bone marrow