Phenotypes associated with this allele

• Allele Symbol: Trp53^tm1Ldo
• Allele Name: targeted mutation 1, Lawrence A Donehower
• Allele ID: MGI:2159430
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Trp53^tm1Ldo/Trp53^+	B6.129S7-Trp53^tm1Ldo	MGI:3814544
ht2	Trp53^tm1Ldo/Trp53^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3814539
ht3	Trp53^tm1Brd/Trp53^tm1Ldo	involves: 129S7/SvEvBrd * C57BL/6	MGI:3814538

Genotype
MGI:3814544

ht1

• Allelic Composition: Trp53^tm1Ldo/Trp53⁺
• Genetic Background: B6.129S7-Trp53^tm1Ldo

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

homeostasis/metabolism

decreased circulating insulin-like growth factor I level ( J:130123 )

• serum IGF-1 levels are 34% of wild-type

endocrine/exocrine glands

abnormal mammary gland development ( J:130123 )

♀ • at 8, 12 and 24 weeks of age, mammary duct outgrowth is reduced compared to in wild-type mice

♀ • however, proliferation and apoptosis are normal throughout development, pregnancy and involution and treatment with hormones or by cross mice to Tg(TTR-Igf1)1Jxu mice rescues outgrowth

♀ • wild type mammary tissue transplanted into mice exhibits reduced outgrowth

♀ • serial transplants of mammary epithelium exhibit decreased transplant capabilities compared to wild-type epithelium

integument

abnormal mammary gland development ( J:130123 )

♀ • at 8, 12 and 24 weeks of age, mammary duct outgrowth is reduced compared to in wild-type mice

♀ • however, proliferation and apoptosis are normal throughout development, pregnancy and involution and treatment with hormones or by cross mice to Tg(TTR-Igf1)1Jxu mice rescues outgrowth

♀ • wild type mammary tissue transplanted into mice exhibits reduced outgrowth

♀ • serial transplants of mammary epithelium exhibit decreased transplant capabilities compared to wild-type epithelium

Genotype
MGI:3814539

ht2

• Allelic Composition: Trp53^tm1Ldo/Trp53⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:73757 )

• old mice treated with Avertin or 5-fluorouracil exhibit increased mortality compared to similarly treated wild-type mice

premature death ( J:73757 )

• median lifespan is 96 weeks compared to 118 weeks for wild-type mice

premature aging ( J:73757 )

• mice exhibit some phenotypes associated with premature ageing

• however, mice do not exhibit liver pathologies, hair graying, alopecia, atrophy of intestinal villi, skin ulcerations, amyloid depositions, brain atrophy, joint disease or cataracts

respiratory system

increased lung adenoma incidence ( J:73757 )

• one mouse develops a lung adenoma and another a well-differentiated bronchio-alveolar lung adenocarcinoma

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:73757 )

• following treatment with 5-fluorouracil, mice that survive fail to exhibit a robust recovery as do wild-type mice

increased susceptibility to xenobiotic induced morbidity/mortality ( J:73757 )

• old mice treated with Avertin or 5-fluorouracil exhibit increased mortality compared to similarly treated wild-type mice

delayed wound healing ( J:73757 )

• in old mice

neoplasm

increased lung adenoma incidence ( J:73757 )

• one mouse develops a lung adenoma and another a well-differentiated bronchio-alveolar lung adenocarcinoma

decreased tumor incidence ( J:73757 )

• mice do not develop any life-threatening tumors over the course of their lifespan compared to 45% of wild-type mice

skeleton

lordokyphosis ( J:73757 )

• by 18 months of age, mice exhibit lordokyphosis

decreased bone mineral density ( J:73757 )

• at 24 months of age

muscle

decreased skeletal muscle mass ( J:73757 )

• at 24 months of age, mean quadriceps mass is 2.5-fold lower than in wild-type mice

muscular atrophy ( J:73757 )

• in older mice

reproductive system

decreased testis weight ( J:73757 )

♂ • at 24 months of age

testis hypoplasia ( J:73757 )

♂ • at 24 months of age

renal/urinary system

decreased kidney weight ( J:73757 )

• at 24 months of age

renal hypoplasia ( J:73757 )

• at 24 months of age

liver/biliary system

decreased liver weight ( J:73757 )

• at 24 months of age

liver hypoplasia ( J:73757 )

• at 24 months of age

immune system

decreased spleen weight ( J:73757 )

• at 24 months of age

spleen hypoplasia ( J:73757 )

• at 24 months of age

growth/size/body

weight loss ( J:73757 )

• by 18 months of age

behavior/neurological

lethargy ( J:73757 )

• at 24 months of age

cellular

abnormal cell physiology ( J:73757 )

• mouse embryonic fibroblasts are 2 to 4 fold more resistant to transformation than wild-type cells

endocrine/exocrine glands

decreased testis weight ( J:73757 )

♂ • at 24 months of age

testis hypoplasia ( J:73757 )

♂ • at 24 months of age

hematopoietic system

decreased spleen weight ( J:73757 )

• at 24 months of age

spleen hypoplasia ( J:73757 )

• at 24 months of age

adipose tissue

decreased subcutaneous adipose tissue amount ( J:73757 )

• at 24 months of age, mice display reduced adipose deposition compared to wild-type mice

integument

decreased subcutaneous adipose tissue amount ( J:73757 )

• at 24 months of age, mice display reduced adipose deposition compared to wild-type mice

sparse hair ( J:73757 )

delayed hair regrowth ( J:73757 )

• by 22 to 24 months of age, no hair growth is observed

thin dermal layer ( J:73757 )

• at 24 months of age

Genotype
MGI:3814538

ht3

• Allelic Composition: Trp53^tm1Brd/Trp53^tm1Ldo
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:73757 )

• mice survive 9 to 10 months

neoplasm

increased tumor incidence ( J:73757 )

• tumorigenesis is slightly delayed compared to in Trp53^tm1Brd homozygotes but mice still exhibit an increase in the numbers of T-cell lymphomas and soft tissue sarcomas compared to in wild-type mice

increased T cell derived lymphoma incidence ( J:73757 )

increased sarcoma incidence ( J:73757 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:73757 )