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Phenotypes Associated with This Genotype
Genotype
MGI:3686897
Allelic
Composition
Sirt6tm1Fwa/Sirt6tm1Fwa
Genetic
Background
involves: 129S6/SvEvTac * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt6tm1Fwa mutation (1 available); any Sirt6 mutation (33 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• fail to thrive and die around P24

cellular
• increased sensitivity of MEFs to monofunctional alkylating agents suggesting a defect in base excision repair; however double strand break repair and nucleotide excision repair are similar to wild-type
• increased DNA damage and reduced survival in MEFs and ES cells following exposure to ionizing radiation; however, UV sensitivity of MEFs is similar to wild-type cells
• thymocytes from 21 day old mice display increased sensitivity to IR and monofunctional alkylating agents; however sensitivity of cells from 12 day old mice is similar to wild-type
• in MEFs and ES cells
• increase in the frequency of fragmented chromosome, detached centromeres and chromosomal gaps in metaphase spreads from early and late passage MEFs
• spectral karyotype analysis detects increases in the frequency of chromosome breaks, translocations, and dicentric chromosomes

growth/size/body
• significantly smaller by about 10 days of age
• decreased body weight as compared to controls at 3 weeks of age on standard diet
• decreased body length as compared to controls at 3 weeks of age on standard diet
• similar size at birth but significantly smaller by about 10 days of age; however food intake is normal

adipose tissue
• acute loss beginning around 3 weeks of age

digestive/alimentary system
• consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age

hematopoietic system
• 10-fold reduction in the number of splenic lymphoctes
• 10-fold reduction in the number of B cell progenitors in the bone marrow
• 50-fold reduction in the thymus
• 10-fold reduction in the number of B cell progenitors in the bone marrow
• severe lymphopenia associated with increased lymphocyte apoptosis
• adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect
• 10-fold reduction in the number of splenic lymphocytes

homeostasis/metabolism
• decreases rapidly in mice older than 12 days of age, dropping below detection limits by 24 days of age
• serum levels of insulin like growth factor (IGF1) are low at 12 days of age and severely by 19 days of age

skeleton
• lordokyphosis visible around 3 weeks of age
• 30% reduction in bone mineral density at about 3 weeks of age

immune system
• consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age
• 10-fold reduction in the number of splenic lymphoctes
• 10-fold reduction in the number of B cell progenitors in the bone marrow
• 50-fold reduction in the thymus
• severe lymphopenia associated with increased lymphocyte apoptosis
• adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect
• 10-fold reduction in the number of splenic lymphocytes

integument
• acute loss beginning around 3 weeks of age

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
progeria DOID:3911 OMIM:176670
J:112817


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
09/27/2022
MGI 6.21
The Jackson Laboratory