Phenotypes associated with this allele

• Allele Symbol: Trp53^tm2.1Tyj
• Allele Name: targeted mutation 2.1, Tyler Jacks
• Allele ID: MGI:3039264
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Trp53^tm2.1Tyj/Trp53^+	involves: 129S4/SvJae	MGI:3584463
ht2	Trp53^tm1Tyj/Trp53^tm2.1Tyj	involves: 129S2/SvPas * 129S4/SvJae	MGI:3584464
cn3	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm2.1Tyj/Trp53^tm2.1Tyj Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * 129S4/SvJae * C57BL/6 * DBA/2	MGI:6448984
cn4	Apc^Min/Apc^+ Trp53^tm2.1Tyj/Trp53^tm2.1Tyj Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2	MGI:6448989
cn5	Rps14^tm1.1Ble/Rps14^+ Tg(Mx1-cre)1Cgn/0 Trp53^tm2.1Tyj/Trp53^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6NTac * CBA/J	MGI:6148310
cn6	Kras^tm4Tyj/Kras^+ Rab11fip1^tm1.1Jicn/Rab11fip1^tm1.1Jicn Tg(Pdx1-cre)6Tuv/0 Trp53^tm2.1Tyj/Trp53^+	involves: 129S4/SvJae * FVB/N	MGI:6113915
cn7	Epha2^tm1Jrui/Epha2^tm1Jrui Kras^tm4Tyj/Kras^+ Trp53^tm2.1Tyj/Trp53^+ Tg(Pdx1-cre)6Tuv/0	involves: 129S/SvEv * 129S4/SvJae * FVB/N	MGI:6113916

Genotype
MGI:3584463

ht1

• Allelic Composition: Trp53^tm2.1Tyj/Trp53⁺
• Genetic Background: involves: 129S4/SvJae

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

mortality/aging

premature death ( J:95316 )

• mean life span is 15.2 months

neoplasm

increased metastatic potential ( J:95316 )

• tumors metastisize more frequently than those in Trp53^tm1Tyj or Trp53^tm3.1Tyj heterozygotes

cellular

decreased cellular sensitivity to gamma-irradiation ( J:95316 )

• resistance to gamma-irradiation induced apoptosis is increased compared to Trp53^tm1Tyj heterozygotes

increased cell proliferation ( J:95316 )

• a larger fraction of MEFs are in S phase compared to Trp53^tm1Tyj hterozygotes; however DNA damage-induced G1 arrest is intact

skeleton

osteopetrosis ( J:95316 )

• diffuse osteopetrosis is frequently observed with osteosarcomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Li-Fraumeni syndrome		DOID:3012	OMIM:PS151623	J:95316

Genotype
MGI:3584464

ht2

• Allelic Composition: Trp53^tm1Tyj/Trp53^tm2.1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae

mortality/aging

premature death ( J:95316 )

• mean life span is 4.5 months

prenatal lethality, incomplete penetrance ( J:95316 )

• a slight decrease is seen in the number of females born

neoplasm

increased tumor incidence ( J:95316 )

• 57% have multiple tumors, significantly more than in Trp53^tm1Tyj homozygotes (32%)

increased T cell derived lymphoma incidence ( J:95316 )

• a slight decrease in hematological malignancies (primarily T cell lymphomas) is seen compared to Trp53^tm1Tyj homozygotes (50% compared to 66%)

increased carcinoma incidence ( J:95316 )

• carcinomas are seen in 16% of mice, with most carcinomas showing signs of invasion, metastasis, or other features of advanced human carcinomas

• most carcinomas are derived from epithelial cells

increased hemangiosarcoma incidence ( J:95316 )

• the incidence of hemangiosarcomas is increased to 62% compared to 32% in Trp53^tm1Tyj homozygotes and these tumors are highly aggressive

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:95316 )

• a slight decrease in hematological malignancies (primarily T cell lymphomas) is seen compared to Trp53^tm1Tyj homozygotes (50% compared to 66%)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Li-Fraumeni syndrome		DOID:3012	OMIM:PS151623	J:95316

Genotype
MGI:6448984

cn3

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm2.1Tyj/Trp53^tm2.1Tyj; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * 129S4/SvJae * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:291671 )

N • jejunal and ileal organoids exhibit normal organoid differentiation and proliferation

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

• treatment of organoids with gallic acid a reversible increase in proliferation of enterocytes unlike in untreated cells that exhibit normal organoid differentiation and proliferation

• however, antibiotic treatment to eliminate gut bacteria rescues hyperproliferation proliferation defect

abnormal enterocyte morphology ( J:291671 )

• dysplastic in the colon and ileum, but not the duodenum and jejunum

• distal gut dysplasia appears earlier than in mice with null Trp53

• mice treated with gallic acid exhibit high-grade dysplastic foci unlike untreated mice\

• however, antibiotic treatment to eliminate gut bacteria results in shorter crypts and better organized villi

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

• treatment of organoids with gallic acid a reversible increase in proliferation of enterocytes unlike in untreated cells that exhibit normal organoid differentiation and proliferation

• however, antibiotic treatment to eliminate gut bacteria rescues hyperproliferation proliferation defect

Genotype
MGI:6448989

cn4

• Allelic Composition: Apc^Min/Apc⁺; Trp53^tm2.1Tyj/Trp53^tm2.1Tyj; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2

neoplasm

decreased alimentary system tumor incidence ( J:291671 )

• reduced tumor burden in the proximal gastrointestinal tract compared with Apc^Min heterozygotes

• however, treatment with gallic acid abolishes the tumor suppressive effect of the mutant Trp53

increased intestinal adenoma incidence ( J:291671 )

• as in Apc^Min heterozygotes with enhancement of tumorigenesis in the colon but reduced tumor burden in the proximal gastrointestinal tract

increased colon adenoma incidence ( J:291671 )

• enhancement of tumorigenesis in the colon compared with Apc^Min heterozygotes

digestive/alimentary system

decreased alimentary system tumor incidence ( J:291671 )

• reduced tumor burden in the proximal gastrointestinal tract compared with Apc^Min heterozygotes

• however, treatment with gallic acid abolishes the tumor suppressive effect of the mutant Trp53

increased intestinal adenoma incidence ( J:291671 )

• as in Apc^Min heterozygotes with enhancement of tumorigenesis in the colon but reduced tumor burden in the proximal gastrointestinal tract

increased colon adenoma incidence ( J:291671 )

• enhancement of tumorigenesis in the colon compared with Apc^Min heterozygotes

Genotype
MGI:6148310

cn5

• Allelic Composition: Rps14^tm1.1Ble/Rps14⁺; Tg(Mx1-cre)1Cgn/0; Trp53^tm2.1Tyj/Trp53⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6NTac * CBA/J

hematopoietic system

hematopoietic system phenotype ( J:233322 )

N • erythropoietic recovery and spleen size after induction of acute hemolytic stress with 25 mg/kg phenylhydrazine

N • no mortality after induction of acute hemolytic stress with high-dose (35 mg/kg) phenylhydrazine

immune system

immune system phenotype ( J:233322 )

N • spleen size after induction of acute hemolytic stress with 25 mg/kg phenylhydrazine

mortality/aging

mortality/aging ( J:233322 )

N • no mortality after induction of acute hemolytic stress with high-dose (35 mg/kg) phenylhydrazine

Genotype
MGI:6113915

cn6

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Rab11fip1^tm1.1Jicn/Rab11fip1^tm1.1Jicn; Tg(Pdx1-cre)6Tuv/0; Trp53^tm2.1Tyj/Trp53⁺
• Genetic Background: involves: 129S4/SvJae * FVB/N

neoplasm

neoplasm ( J:244261 )

N • phenotypes are relative to the control KPC (Kras^G12D/+, p53^R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice

N • size of PDAC primary tumors same as control

decreased metastatic potential ( J:244261 )

• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues

• reduced migration of PDAC cells in vitro

mortality/aging

mortality/aging ( J:244261 )

N • survival same as control

Genotype
MGI:6113916

cn7

• Allelic Composition: Epha2^tm1Jrui/Epha2^tm1Jrui; Kras^tm4Tyj/Kras⁺; Trp53^tm2.1Tyj/Trp53⁺; Tg(Pdx1-cre)6Tuv/0
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * FVB/N

neoplasm

neoplasm ( J:244261 )

N • phenotypes are relative to the control KPC (Kras^G12D/+, p53^R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice

N • size of PDAC primary tumors same as control

decreased metastatic potential ( J:244261 )

• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues

• reduced migration of PDAC cells in vitro

mortality/aging

abnormal survival ( J:244261 )

• survival reduced compared to control