Phenotypes Associated with This Genotype

Genotype
MGI:3686897

• Allelic Composition: Sirt6^tm1Fwa/Sirt6^tm1Fwa
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

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

mortality/aging

lethality at weaning, complete penetrance ( J:112817 )

• fail to thrive and die around P24

cellular

increased cellular sensitivity to alkylating agents ( J:112817 )

• 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 cellular sensitivity to ionizing radiation ( J:112817 )

• 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

decreased cell proliferation ( J:112817 )

• in MEFs and ES cells

spontaneous chromosome breakage ( J:112817 )

• 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

decreased body size ( J:112817 )

• significantly smaller by about 10 days of age

decreased body weight ( J:229077 )

• decreased body weight as compared to controls at 3 weeks of age on standard diet

decreased body length ( J:229077 )

• decreased body length as compared to controls at 3 weeks of age on standard diet

postnatal growth retardation ( J:112817 )

• similar size at birth but significantly smaller by about 10 days of age; however food intake is normal

adipose tissue

decreased subcutaneous adipose tissue amount ( J:112817 )

• acute loss beginning around 3 weeks of age

digestive/alimentary system

colitis ( J:112817 )

• consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age

hematopoietic system

abnormal lymphopoiesis ( J:112817 )

• 10-fold reduction in the number of splenic lymphoctes

abnormal B cell differentiation ( J:112817 )

• 10-fold reduction in the number of B cell progenitors in the bone marrow

decreased double-positive T cell number ( J:112817 )

• 50-fold reduction in the thymus

decreased bone marrow cell number ( J:112817 )

• 10-fold reduction in the number of B cell progenitors in the bone marrow

decreased leukocyte cell number ( J:112817 )

• severe lymphopenia associated with increased lymphocyte apoptosis

• adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect

spleen hypoplasia ( J:112817 )

• 10-fold reduction in the number of splenic lymphocytes

homeostasis/metabolism

decreased circulating glucose level ( J:112817 )

• decreases rapidly in mice older than 12 days of age, dropping below detection limits by 24 days of age

decreased circulating insulin-like growth factor I level ( J:112817 )

• serum levels of insulin like growth factor (IGF1) are low at 12 days of age and severely by 19 days of age

skeleton

lordokyphosis ( J:112817 )

• lordokyphosis visible around 3 weeks of age

decreased bone mineral density ( J:112817 )

• 30% reduction in bone mineral density at about 3 weeks of age

immune system

colitis ( J:112817 )

• consisting of erosion of the superficial colonic epithelium beginning around 3 weeks of age

abnormal lymphopoiesis ( J:112817 )

• 10-fold reduction in the number of splenic lymphoctes

abnormal B cell differentiation ( J:112817 )

• 10-fold reduction in the number of B cell progenitors in the bone marrow

decreased double-positive T cell number ( J:112817 )

• 50-fold reduction in the thymus

decreased leukocyte cell number ( J:112817 )

• severe lymphopenia associated with increased lymphocyte apoptosis

• adoptive transfer studies indicate increased lymphocyte apoptosis is not a cell intrinsic defect

spleen hypoplasia ( J:112817 )

• 10-fold reduction in the number of splenic lymphocytes

integument

decreased subcutaneous adipose tissue amount ( J:112817 )

• 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