All Phenotypes Sirt1<tm1.1Cxd> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sirt1^tm1.1Cxd/Sirt1^tm1.1Cxd	either: (involves: 129S6/SvEvTac * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * C57BL/6 * FVB/N)	MGI:3812160
ht2	Sirt1^tm1.1Cxd/Sirt1⁺	either: (involves: 129S6/SvEvTac * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * C57BL/6 * FVB/N)	MGI:3812163
cx3	Sirt1^tm1.1Cxd/Sirt1^tm1.1Cxd Trp53^tm1Brd/Trp53^tm1Brd	either: (involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N)	MGI:3812167
cx4	Sirt1^tm1.1Cxd/Sirt1^tm1.1Cxd Trp53^tm1Brd/Trp53⁺	either: (involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N)	MGI:3812169
cx5	Sirt1^tm1.1Cxd/Sirt1⁺ Trp53^tm1Brd/Trp53⁺	either: (involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N)	MGI:3812172

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

mortality/aging

decreased survivor rate ( J:140089 )

• Background Sensitivity: the survival rate to adulthood on a 129S6/SvEv FVB background is 1% while the survival rate on a 129S6/SvEv FVB Black Swiss is 9.3%

lethality throughout fetal growth and development, incomplete penetrance ( J:140089 )

• nearly all mice die between E14.5 and E16.5

embryonic lethality during organogenesis, incomplete penetrance ( J:140089 )

• mice begin to die at E9.5

cellular

abnormal chromosome morphology ( J:140089 )

• cells from E9.5 mice exhibit chromosomal abnormalities including aneuploidy, broken chromosomes and less condensed chromosomes

• heterochromatin formation is impaired

aneuploidy ( J:140089 )

• in 37% of mouse embryo fibroblasts

abnormal cell cycle checkpoint function ( J:140089 )

• following treatment with low dose of gamma irradiation, mouse embryonic fibroblasts exhibit a defect in the G1/S checkpoint

• however, at high doses of radiation the G1/S checkpoint functions normally

increased mitotic index ( J:140089 )

• embryos exhibit an increase in the number of cells in the early phase of mitosis

abnormal cell death ( J:140089 )

• embryos exhibit an increase in the number of cells positive for markers of cell death

increased cellular sensitivity to gamma-irradiation ( J:140089 )

• survival of mouse embryonic fibroblasts followed exposure to gamma radiation is decrease compared to in similarly treated wild-type cells

increased cellular sensitivity to ultraviolet irradiation ( J:140089 )

• survival of mouse embryonic fibroblasts followed exposure to UV radiation is decrease compared to in similarly treated wild-type cells

abnormal DNA repair ( J:140089 )

• mouse embryonic fibroblasts exhibit reduced microhomologous DNA damage repair ability compared to in wild-type cells

• mouse embryonic fibroblasts exhibit defects in repair of UV irradiation damage

• however, less precise ligation and end joining is normal

abnormal DNA replication ( J:140089 )

• 37% of mouse embryo fibroblasts exhibit lagging chromosomes and unequal segregation during replication

embryo

decreased embryo size ( J:140089 )

• most embryos at E10.5 to E12.5

absent hindlimb buds ( J:140089 )

• at E11.25, some mice lack hindlimb buds

growth/size/body

decreased embryo size ( J:140089 )

• most embryos at E10.5 to E12.5

abnormal head morphology ( J:140089 )

• in some surviving mice at E11.25

homeostasis/metabolism

abnormal DNA repair ( J:140089 )

• mouse embryonic fibroblasts exhibit reduced microhomologous DNA damage repair ability compared to in wild-type cells

• mouse embryonic fibroblasts exhibit defects in repair of UV irradiation damage

• however, less precise ligation and end joining is normal

abnormal DNA replication ( J:140089 )

• 37% of mouse embryo fibroblasts exhibit lagging chromosomes and unequal segregation during replication

limbs/digits/tail

absent hindlimb buds ( J:140089 )

• at E11.25, some mice lack hindlimb buds

Allelic Composition	Sirt1^tm1.1Cxd/Sirt1⁺
Genetic Background	either: (involves: 129S6/SvEvTac * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * C57BL/6 * FVB/N)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1^tm1.1Cxd mutation (0 available); any Sirt1 mutation (78 available)

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

nervous system

exencephaly ( J:140089 )

• in some mice

Allelic Composition	Sirt1^tm1.1Cxd/Sirt1^tm1.1Cxd Trp53^tm1Brd/Trp53^tm1Brd
Genetic Background	either: (involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sirt1^tm1.1Cxd mutation (0 available); any Sirt1 mutation (78 available)
Trp53^tm1Brd mutation (5 available); any Trp53 mutation (232 available)

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:140089 )

• some mice die between E16.5 and birth

perinatal lethality, incomplete penetrance ( J:140089 )

• only one mouse survives birth

postnatal lethality, complete penetrance ( J:140089 )

• no mice are alive at weaning

embryonic lethality, incomplete penetrance ( J:140089 )

• fewer than expected mice are alive at E15.5

Allelic Composition	Sirt1^tm1.1Cxd/Sirt1^tm1.1Cxd Trp53^tm1Brd/Trp53⁺
Genetic Background	either: (involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N)

Find Mice

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

mortality/aging

decreased survivor rate ( J:140089 )

• 5 mice are alive at weaning

perinatal lethality, incomplete penetrance ( J:140089 )

• fewer than expected mice survive to birth

embryonic lethality, incomplete penetrance ( J:140089 )

• fewer than expected mice are alive at E15.5

Allelic Composition	Sirt1^tm1.1Cxd/Sirt1⁺ Trp53^tm1Brd/Trp53⁺
Genetic Background	either: (involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB/N) or (involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB/N)

Find Mice

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

neoplasm

abnormal tumor morphology ( J:140089 )

• tumors exhibit extensive aneuploidy and chromosomal aberrations, notably translocations, chromosome breaks, deletions and dicentric chromosomes

increased tumor incidence ( J:140089 )

• mice begin to develop tumors at 5 months of age with tumor incidence reaching 76% by 20 months of age compared to only 2 of 21 Sirt1^tm1.1Cxd heterozygotes and 3 of 23 Trp53^tm1Brd heterozygotes

• however, treatment of mice with resveratrol decreases the incidence of tumors and delays onset

increased lymphoma incidence ( J:140089 )

• 35% of tumors are lymphomas

increased carcinoma incidence ( J:140089 )

• 16% of tumors are carcinomas

increased sarcoma incidence ( J:140089 )

• 46% of tumors are sarcomas

increased teratoma incidence ( J:140089 )

• 22% of tumors are teratomas

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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