Strain Detail Sheet

Strain Name: B6.129X1-Trp53tm1Ldo/Mmnc

Stock Number: 000362-UNC

Other Names:

Gene Details: (provided by MGI)

Allele Symbol: Trp53tm1Ldo
Name: targeted mutation 1, Lawrence A Donehower
Alteration at locus: Knockout

Genetic Alterations:
Exons 1-6 of the p53 gene are deleted as well as about 500 kb of upstream sequence. The upstream Vamp2 promoter is juxtaposed next to exons 7-11 of p53 to generate a chimeric message that produces a C-terminal truncated p53 protein.

Genotype Determination:

ES Cell Line: AB1 derived from C57BL/6J

Strain Description

Phenotype
p53+/m are normal up to the age of about 12 months. From 14-18 months of age, the mutant mice begin to exhibit early aging phenotypes and resistance to spontaneous cancers. Early aging phenotypes include reduced longevity, osteoporosis, atrophy of skeletal muscle, skin, and many organs, and reduced tolerance for stresses.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Trp53tm1Ldo/Trp53+
        B6.129S7-Trp53<tm1Ldo>
  • reproductive system phenotype
    • abnormal mammary gland development (MGI Ref ID 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
  • homeostasis/metabolism phenotype
    • decreased circulating insulin-like growth factor I level (MGI Ref ID J:130123)
      • serum IGF-1 levels are 34% of wild-type
  • endocrine/exocrine gland phenotype
    • abnormal mammary gland development (MGI Ref ID 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 phenotype
    • abnormal mammary gland development (MGI Ref ID J:130123)
      • at 8, 12 and 24 weeks of age, mammary duct outgrowth is reduce d 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


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Trp53tm1Ldo/Trp53+
        involves: 129S7/SvEvBrd * C57BL/6
  • mortality/aging
    • increased sensitivity to xenobiotic induced morbidity/mortality (MGI Ref ID J:73757)
      • old mice treated with Avertin or 5-fluorouracil exhibit increased mortality compared to similarly treated wild-type mice
    • premature aging (MGI Ref ID 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
    • premature death (MGI Ref ID J:73757)
      • median lifespan is 96 weeks compared to 118 weeks for wild-type mice
  • homeostasis/metabolism phenotype
    • abnormal physiological response to xenobiotic (MGI Ref ID J:73757)
      • following treatment with 5-fluorouracil, mice that survive fail to exhibit a robust recovery as do wild-type mice
      • increased sensitivity to xenobiotic induced morbidity/mortality (MGI Ref ID J:73757)
        • old mice treated with Avertin or 5-fluorouracil exhibit increased mortality compared to similarly treated wild-type mice
    • delayed wound healing (MGI Ref ID J:73757)
      • in old mice
  • tumorigenesis
    • decreased tumor incidence (MGI Ref ID J:73757)
      • mice do not develop any life-threatening tumors over the course of their lifespan compared to 45% of wild-type mice
    • increased lung adenoma incidence (MGI Ref ID J:73757)
      • one mouse develops a lung adenoma and another a well-differentiated bronchio-alveolar lung adenocarcinoma
  • skeleton phenotype
    • decreased bone mineral density (MGI Ref ID J:73757)
      • at 24 months of age
    • kyphosis (MGI Ref ID J:73757)
      • by 18 months of age, mice exhibit lordokyphosis
    • lordosis (MGI Ref ID J:73757)
      • by 18 months of age, mice exhibit lordokyphosis
  • muscle phenotype
    • decreased skeletal muscle mass (MGI Ref ID J:73757)
      • at 24 months of age, mean quadriceps mass is 2.5-fold lower than in wild-type mice
    • muscular atrophy (MGI Ref ID J:73757)
      • in older mice
  • reproductive system phenotype
    • decreased testis weight (MGI Ref ID J:73757)
      • at 24 months of age
    • testis hypoplasia (MGI Ref ID J:73757)
      • at 24 months of age
  • renal/urinary system phenotype
    • decreased kidney weight (MGI Ref ID J:73757)
      • at 24 months of age
    • renal hypoplasia (MGI Ref ID J:73757)
      • at 24 months of age
  • liver/biliary system phenotype
    • decreased liver weight (MGI Ref ID J:73757)
      • at 24 months of age
    • liver hypoplasia (MGI Ref ID J:73757)
      • at 24 months of age
  • immune system phenotype
    • decreased spleen weight (MGI Ref ID J:73757)
      • at 24 months of age
    • spleen hypoplasia (MGI Ref ID J:73757)
      • at 24 months of age
  • growth/size phenotype
    • weight loss (MGI Ref ID J:73757)
      • by 18 months of age
  • behavior/neurological phenotype
    • lethargy (MGI Ref ID J:73757)
      • at 24 months of age
  • cellular phenotype
    • abnormal cell physiology (MGI Ref ID J:73757)
      • mouse embryonic fibroblasts are 2 to 4 fold more resistant to transformation than wild-type cells
  • endocrine/exocrine gland phenotype
    • decreased testis weig ht (MGI Ref ID J:73757)
      • at 24 months of age
    • testis hypoplasia (MGI Ref ID J:73757)
      • at 24 months of age
  • hematopoietic system phenotype
    • decreased spleen weight (MGI Ref ID J:73757)
      • at 24 months of age
    • spleen hypoplasia (MGI Ref ID J:73757)
      • at 24 months of age
  • adipose tissue phenotype
    • decreased subcutaneous adipose tissue amount (MGI Ref ID J:73757)
      • at 24 months of age, mice display reduced adipose deposition compared to wild-type mice
  • integument phenotype
    • decreased subcutaneous adipose tissue amount (MGI Ref ID J:73757)
      • at 24 months of age, mice display reduced adipose deposition compared to wild-type mice
    • delayed hair regrowth (MGI Ref ID J:73757)
      • by 22 to 24 months of age, no hair growth is observed
    • sparse hair (MGI Ref ID J:73757)
    • thin dermal layer (MGI Ref ID J:73757)
      • at 24 months of age

Founder genetic background: 129X1/SvJ

Strain genetic background: C57BL/6J

Suggested Control Mice:

  • Wildtype littermates

Research Applications

  • Cancer
  • Accelerated or premature aging

Strain Origin

Donor: Larry Donehower, Ph.D., Baylor College of Medicine

Primary Reference:

Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Hee Park S, Thompson T, Karsenty G, Bradley A, Donehower LA. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002 Jan 3;415(6867):45-53. (Medline PMID: 11780111 )

Colony and Husbandry Information

Appearance

Coat color: Black

Other:


Breeding

MMRRC Breeding System: Intra strain mating

Breeding Scheme(s):

  • Heterozygous female x Wildtype male
  • Wildtype female x Heterozygous male

Generation: N5

Overall Breeding Performance: Normal

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
 
Age Reproductive Decline: 16 weeks 16 weeks

Average litter size: 6 -8

Recommended wean age: 3 weeks

Special Considerations

None

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.

Order Request Information

Availability Level:

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution:

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Fees:

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description
Distribution
Fee/unit (US $)		 Units Notes
000362-UNC-RESUSLitter recovered from cryo-archive
$2,022.00 / $4,109.00
Non-Profit / For-Profit
 Litter Recovered litter1; additional fees for any special requests.

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the "Request this Strain" button above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.

The MMRRC is a collaborative effort, funded by grants from the NIH

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