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Phenotypes Associated with This Genotype
Genotype
MGI:3665480
Allelic
Composition
Wrntm1Led/Wrntm1Led
Genetic
Background
B6.129S6(BKSW)-Wrntm1Led
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Wrntm1Led mutation (0 available); any Wrn mutation (54 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 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
• at 9 months, homozygotes fed a 5% fat diet show an abnormal increase in visceral fat deposition relative to wild-type mice
• 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
• 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
• 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
• 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
• at 4 months, male (but not female) homozygotes exhibit a 67% increase in serum hyaluronic acid levels relative to wild-type counterparts
• 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
• 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
• 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
• 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/dtmax) and a reduced ejection time, indicating early signs of compensated cardiac functional hypertrophy at 12 months
• 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
• at 12 months, male homozygotes exhibit an increased ventricular systolic pressure relative to wild-type males
• at 12 months, male homozygotes exhibit a reduced aortic diastolic pressure relative to wild-type males

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


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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last database update
05/10/2022
MGI 6.19
The Jackson Laboratory