All Phenotypes Wrn<tm1Led> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wrn^tm1Led/Wrn^tm1Led	B6.129S6(BKSW)-Wrn^tm1Led	MGI:3665480
hm2	Wrn^tm1Led/Wrn^tm1Led	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * NIH Black Swiss)	MGI:2383958
hm3	Wrn^tm1Led/Wrn^tm1Led	involves: 129S6/SvEvTac * Black Swiss	MGI:3665481
ht4	Wrn^tm1Led/Wrn⁺	involves: 129S6/SvEvTac * Black Swiss	MGI:3665482
cx5	Trp53^tm1Brd/Trp53^tm1Brd Wrn^tm1Led/Wrn^tm1Led	either: (involves: 129S/SvEv) or (involves: 129S/SvEv * NIH Black Swiss)	MGI:2383960
cx6	Cdkn1a^tm1Led/Cdkn1a^tm1Led Wrn^tm1Led/Wrn^tm1Led	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * NIH Black Swiss)	MGI:2383959
cx7	Tg(Hba-x-v-Ha-ras)TG.ACLed/0 Wrn^tm1Led/Wrn^tm1Led	involves: 129 * FVB/N * Black Swiss	MGI:2651804

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

growth/size/body

increased susceptibility to age related obesity ( J:106446 )

• at 5 months, all homozygotes (esp. virgin females) fed a 5% fat diet show a greater increase in body weight relative to similarly fed wild-type littermates; no differences in body weight are observed up to 4 months of age

• at 5 months, mutant virgin females exhibit a 25% increase in body weight, whereas mutant males show only a 12% increase in body weight relative to wild-type mice

adipose tissue

increased abdominal adipose tissue amount ( J:106446 )

• at 9 months, homozygotes fed a 5% fat diet show an abnormal increase in visceral fat deposition relative to wild-type mice

increased inguinal fat pad weight ( J:106446 )

• at 9 months, female and male homozygotes fed a 5% fat diet show a 4-fold and 2.5-fold increase in inguinal (subcutaneous) white adipose mass, respectively, relative to wild-type counterparts

increased retroperitoneal fat pad weight ( J:106446 )

• at 9 months, female and male homozygotes fed a 5% fat diet show a similar 3-fold increase in visceral (retroperitoneal) white adipose mass relative to wild-type mice

homeostasis/metabolism

hyperglycemia ( J:106446 )

• aging homozygotes develop hyperglycemia: at 6 and 9 months, both sexes show a similar 10% and 25% increase in fasting blood glucose levels, respectively, relative to age-matched wild-type counterparts

increased circulating insulin level ( J:106446 )

• at 6 months (but not at 3 months), female and male homozygotes show a similar 2.4-fold increase in fasting serum insulin levels relative to age-matched wild-type counterparts

increased circulating hyaluronic acid level ( J:106446 )

• at 4 months, male (but not female) homozygotes exhibit a 67% increase in serum hyaluronic acid levels relative to wild-type counterparts

increased circulating cholesterol level ( J:106446 )

• at 6 months, virgin female homozygotes show a 44% increase in fasting total cholesterol levels relative to wild-type females; no differences are noted at 3 months

• in contrast, male homozygotes show no significant differences in total cholesterol levels or HDL levels relative to wild-type males at 3 or 6 months

increased circulating triglyceride level ( J:106446 )

• at 6 months, female and male homozygotes display a 30% and 19% increase in fasting serum triglyceride levels, respectively, relative to age-matched wild-type counterparts

• however, no significant differences in serum triglyceride levels are observed at 3 or 4 months i.e. prior to the onset of age-related obesity

hyperlipidemia ( J:106446 )

insulin resistance ( J:106446 )

• at 6 months, fasting female and male homozygotes show a similar increase in insulin resistance (2.4-fold higher on the HOMA-IR index) relative to wild-type mice

cardiovascular system

aortic valve stenosis ( J:106446 )

• at 12 months, male homozygotes exhibit signs of aortic stenosis, as shown by a reduced aortic diastolic pressure and an increased ventricular systolic pressure relative to wild-type males

• however, aortic stenosis is compensated by an increased maximal contractility (dP/dt_max) and a reduced ejection time, indicating early signs of compensated cardiac functional hypertrophy at 12 months

cardiac interstitial fibrosis ( J:106446 )

• several aging homozygotes exhibit mild to severe cardiac interstitial fibrosis of the left ventricle on all genetic backgrounds studied, including an inbred 129/Sv, outbred (involving 129/Sv and Black Swiss) and congenic C57BL/6 background

increased left ventricle systolic pressure ( J:106446 )

• at 12 months, male homozygotes exhibit an increased ventricular systolic pressure relative to wild-type males

decreased systemic arterial diastolic blood pressure ( J:106446 )

• at 12 months, male homozygotes exhibit a reduced aortic diastolic pressure relative to wild-type males

cellular

cardiac interstitial fibrosis ( J:106446 )

increased cellular sensitivity to oxidative stress ( J:106446 )

• in vitro, mutant MEFs exhibit a greater increase in ROS levels after exposure to high concentrations of palmitate than wild-type MEFs

oxidative stress ( J:106446 )

• adult, but not juvenile, homozygotes exhibit severe oxidative stress followed by elevated cardiac oxidative DNA damage, all before the onset of cardiac fibrosis

• at 9 months, female homozygotes display a more severe oxidative stress, with a 2-fold higher increase in serum H₂O₂ levels and cardiac tissue reactive oxygen species relative to male homozygotes

• by 12 months, female homozygotes exhibit a 2-fold increase in cardiac oxidative DNA damage relative to wild-type females, not evident at 6 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werner syndrome		DOID:5688	OMIM:277700	J:106446

Allelic Composition	Wrn^tm1Led/Wrn^tm1Led
Genetic Background	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * NIH Black Swiss)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Wrn^tm1Led mutation (0 available); any Wrn mutation (94 available)

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:48424 )

• slightly reduced Mendelian ratio, suggesting some prenatal or early postnatal lethality

neoplasm

increased tumor incidence ( J:48424 )

• 62% of mice at 24 months developed hyperplasias or tumors in one of their organs

Allelic Composition	Wrn^tm1Led/Wrn^tm1Led
Genetic Background	involves: 129S6/SvEvTac * Black Swiss

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Wrn^tm1Led mutation (0 available); any Wrn mutation (94 available)

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

cardiovascular system

cardiac interstitial fibrosis ( J:106446 )

• aging homozygotes of both sexes are more likely to develop severe cardiac fibrosis than wild-type mice; the number of affected male and female homozygotes is similar

• by 25 months (when all mutants are already dead), 65% of homozygotes have developed more severe cardiac interstitial fibrosis of the left ventricle than wild-type littermates (15%); earliest time of onset is at 5 months

• in addition, 5 of 55 homozygotes also exhibit fibrosis around major cardiac vessels or the aortic root

• calculation of cause-specific hazard rates indicates that homozygotes are more likely to develop and die from cardiac fibrosis than cancers or infections, whereas wild-type mice are more likely to die from other diseases

heart inflammation ( J:106446 )

• by 25 months, 5 of 55 homozygotes exhibiting fibrosis of the aortic root also show evidence of inflammation beneath the endothelium

immune system

heart inflammation ( J:106446 )

• by 25 months, 5 of 55 homozygotes exhibiting fibrosis of the aortic root also show evidence of inflammation beneath the endothelium

increased susceptibility to infection ( J:106446 )

• by 25 months of age, homozygotes are likely to suffer from some type of infection

homeostasis/metabolism

abnormal thrombosis ( J:106446 )

• 2 of 55 aging homozygotes exhibit an organized thrombus in a major vessel

neoplasm

increased tumor incidence ( J:106446 )

• by 25 months of age, homozygotes are likely to exhibit neoplasias of some kind

• 17 of 28 female homozygotes develop some type of tumor, with several females dying of cancer before the onset of cardiac fibrosis

• in contrast, only 9 of 27 male homozygotes develop a tumor, indicating that mutant females are more susceptible to tumor formation than males

cellular

cardiac interstitial fibrosis ( J:106446 )

• aging homozygotes of both sexes are more likely to develop severe cardiac fibrosis than wild-type mice; the number of affected male and female homozygotes is similar

• in addition, 5 of 55 homozygotes also exhibit fibrosis around major cardiac vessels or the aortic root

Allelic Composition	Wrn^tm1Led/Wrn⁺
Genetic Background	involves: 129S6/SvEvTac * Black Swiss

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Wrn^tm1Led mutation (0 available); any Wrn mutation (94 available)

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

cardiovascular system

cardiac interstitial fibrosis ( J:106446 )

• by 25 months, 43% of heterozygotes vs 15% of wild-type littermates display cardiac interstitial fibrosis of the left ventricle

• in addition, 1 of 21 heterozygotes also exhibit fibrosis of the aortic root, not observed in wild-type mice

cellular

cardiac interstitial fibrosis ( J:106446 )

• by 25 months, 43% of heterozygotes vs 15% of wild-type littermates display cardiac interstitial fibrosis of the left ventricle

• in addition, 1 of 21 heterozygotes also exhibit fibrosis of the aortic root, not observed in wild-type mice

Allelic Composition	Trp53^tm1Brd/Trp53^tm1Brd Wrn^tm1Led/Wrn^tm1Led
Genetic Background	either: (involves: 129S/SvEv) or (involves: 129S/SvEv * NIH Black Swiss)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Trp53^tm1Brd mutation (5 available); any Trp53 mutation (240 available)
Wrn^tm1Led mutation (0 available); any Wrn mutation (94 available)

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

neoplasm

increased tumor incidence ( J:68488 )

• 50% of mice by the age of 3 months developed tumors

decreased tumor latency ( J:68488 )

• an acceleration of tumorigenesis, in comparison to Wrn^tm1Led homozygous mice

Allelic Composition	Cdkn1a^tm1Led/Cdkn1a^tm1Led Wrn^tm1Led/Wrn^tm1Led
Genetic Background	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * NIH Black Swiss)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Led mutation (1 available); any Cdkn1a mutation (63 available)
Wrn^tm1Led mutation (0 available); any Wrn mutation (94 available)

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

neoplasm

increased tumor incidence ( J:68488 )

• 56% of mice older than 15 months developed hyperplasias or tumors

• no acceleration of tumorigenesis, in comparison to Wrn^tm1Led homozygous mice

Allelic Composition	Tg(Hba-x-v-Ha-ras)TG.ACLed/0 Wrn^tm1Led/Wrn^tm1Led
Genetic Background	involves: 129 * FVB/N * Black Swiss

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Hba-x-v-Ha-ras)TG.ACLed mutation (1 available)
Wrn^tm1Led mutation (0 available); any Wrn mutation (94 available)

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

neoplasm

increased incidence of tumors by chemical induction ( J:79056 )

• increased skin and fore-stomach papilloma incidence after TPA-treatment

increased papilloma incidence ( J:79056 )

• increased fore-stomach papilloma incident with or without TPA-treatment

• increased skin papilloma incidence after TPA-treatment

growth/size/body

weight loss ( J:79056 )

• dramatic weight loss between 6 and 8 months of age

• weight loss accompanies fore-stomach papilloma development

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:79056 )

• increased skin and fore-stomach papilloma incidence after TPA-treatment

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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