Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation N7+5F14 (31-DEC-07)   Donating Investigator Carol Greider,   Johns Hopkins Univ School of Medicine

Description
Early generation mice that are homozygous null for the Terc gene are phenotypically normal. No Terc transcript or telomerase activity is detected. If null mice are maintained as homozygotes, progressive adverse effects on the reproductive and hematopoietic systems are observed. By the fifth generation of homozygous intercrossing, fertility is significantly diminished. Testes size and weight is reduced by ~80%. Germ cells exhibit decreased rates in proliferation and increased rates of apoptosis resulting in a general state of germ cell depletion. Females exhibit smaller ovaries and diminished uterine horns. The proliferative capacity of hematopoietic cells derived from bone marrow and spleen is significantly compromised. Progressive generations of interbreeding the null mice results in progressive telomere shortening (4.8 +/- 2.4 kb per generation). Cells from the fourth generation onward possess chromosome ends lacking detectable telomere repeats, aneuploidy, and chromosomal abnormalities, including end-to-end fusions.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the entire Terc gene. The construct was electroporated into WW6 embryonic stem (ES) cells. WW6 ES cells are derived from a mixed genetic background (C57BL/6J ,129/Sv and SJL). Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Terc^tm1Rdp/Terc^tm1Rdp

        involves: 129/Sv * C57BL/6J * SJL

• lethality-prenatal/perinatal
• prenatal lethality (MGI Ref ID J:53600)
  • a fraction of homozygous embryos from late generation homozygous matings do not survive gestation to completion or die immediately after birth
  • only 74% of homozygous fetuses from late generation pregnant females are alive
• life span-post-weaning/aging
• premature aging (MGI Ref ID J:120065)
  • late generation mutants exhibit accelerated degeneration as indicated by hair graying, alopecia, kyphosis, reduced body size and weight, and fragility
• premature death (MGI Ref ID J:110900)
  • older (6-8 months) fifth generation mutants that show sudden loss in body weight and activity die 7-12 hours after the manifestation of these phenotypes
• cellular phenotype
• abnormal chromosome morphology (MGI Ref ID J:89751)
  • lack of perinuclear distribution of telomeres in fourth generation mutants
• abnormal telomere length (MGI Ref ID J:74001)
  • embryonic fibroblast cells derived from mutant mice after the fourth generation lacked detectable telomeric repeats and were often aneupolid with chromosomal abnormalities, including end to end fusions
  • keratinocytes exhibit a significant decrease in average telomere length compared with wild-type cells
  • splenocytes from non-immunized fifth generation mutants contain shorter telomere lengths than wild-type
  • upon immunization with an antigen, proliferating splenocyte telomeres are shortened during germinal center formation, unlike in wildtype mice which show elongation of telomeres, however telomeres are longer than seen in non-immunized mutants
  • cells from embryos that fail to close the neural tube have shorter telomeres and decreased viability than mutants with a closed neural tube
  • cardiac myocytes of second and fifth generation mutants show telomere shortening, with cardiomyocytes from older mutants having shorter telomeres than in younger mutants
  • telomere shortening occurs in both meiocytes with normal and abnormal synapsis
  • the anaphase bridge index (ABI) is increased in late-generation (G4/G5) intestinal crypts indicating telomere dysfunction
• increased apoptosis (MGI Ref ID J:53600)
  • E10.5 embryos with neural tube defects exhibit an increase in apoptosis
  • apoptosis of male germ cells and in the GI crypts of late generation mutants
• tumorigenesis
• decreased incidence of induced tumors (MGI Ref ID J:74001)
  • fifth generation mutants show decreased tumor growth rate and lower tumor formation efficiency upon dermal or subcutaneous melanoma cell injection
  • tumors that are induced in fifth generation mutants show decreased replication potential and increased apoptotic rates
• decreased incidence of chemically-induced tumors (MGI Ref ID J:96945)
  • first generation mutants are slightly less susceptible to DMBA + TPA induced skin tumorigenesis, with a delay in papilloma formation compared to wild-type and papillomas that do not progress to lesions bigger than 8 mm
• cardiovascular system phenotype
• abnormal angiogenesis (MGI Ref ID J:74001)
  • late generation mutants show decreased angiogenic potential in a basement membrane matrix assay
  • microvessel density is decreased in the induced tumors of fifth generation mutants
  • large abnormal vessels are present in the induced tumors of fifth generation mutants
• abnormal cardiovascular system physiology (MGI Ref ID J:110900)
  • fifth generation, but not second generation, mutants suffer from a severe left ventricular failure
• abnormal cardiac muscle contractility (MGI Ref ID J:110900)
  • fifth generation, but not second generation, mutants exhibit a decrease in +dP/dt
• abnormal cardiac muscle relaxation (MGI Ref ID J:110900)
  • fifth generation mutants exhibit a decrease in -dP/dt
• abnormal fetal cardiomyocyte proliferation (MGI Ref ID J:110900)
  • second and fifth generation mutants exhibit decreased cardiac myocyte proliferation
• congestive heart failure (MGI Ref ID J:110900)
  • older fifth generation mutants die of heart failure
• decreased left ventricular developed pressure (MGI Ref ID J:110900)
  • fifth generation mutants exhibit a decrease in LV developed pressure
• dilated cardiomyopathy (MGI Ref ID J:110900)
  • dilated cardiomyopathy develops in fifth generation mutants
• increased left ventricle diastolic pressure (MGI Ref ID J:110900)
  • fifth generation mutants exhibit an elevation of LV end-diastolic pressure
• abnormal myocardial fiber morphology (MGI Ref ID J:110900)
  • the volume of binucleated cardiomyocytes is increased by 24% in second generation mutants and 52% in fifth generation mutants
  • the volume of mononucleated cardiomyocytes is increased by 39% and 43% in second and fifth generation mutants, respectively
• decreased myocardial fiber number (MGI Ref ID J:110900)
  • cardiomyocyte number is decreased 16% and 49% in second and fifth generation mutants, respectively
• increased cardiomyocyte apoptosis (MGI Ref ID J:110900)
  • fifth generation mutants exhibit a 63% increase in cardiomyocyte apoptosis
• cardiac hypertrophy (MGI Ref ID J:110900)
  • fifth generation mutants exhibit cardiac myocyte hypertrophy
• left ventricle hypertrophy (MGI Ref ID J:110900)
  • fifth generation mutants show a reduction in left ventricle mass that is accompanied by a decrease in left ventricle mass:chamber volume ratio, indicating decompensated eccentric left ventricle hypertrophy in the absence of an absolute increase in ventricular weight
• decreased heart weight (MGI Ref ID J:110900)
  • heart weight is decreased in fifth generation mutants
• decreased left ventricle weight (MGI Ref ID J:110900)
  • left ventricle weight is decreased in fifth generation mutants
• hematopoietic system phenotype
• abnormal spleen B cell follicle morphology (MGI Ref ID J:60223)
  • spleens from sixth generation mutants (but not earlier generations) show fewer follicles
• decreased spleen germinal center number (MGI Ref ID J:60223)
  • fifth and sixth generation homozygotes show a reduction in germinal centers following antigen (KLH) immunization
• decreased B cell proliferation (MGI Ref ID J:60223)
  • splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• decreased T cell proliferation (MGI Ref ID J:60223)
  • splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• increased B cell apoptosis (MGI Ref ID J:60223)
  • splenocytes from immunized fifth and sixth generation mice exhibit a small increase in apoptosis after mitogen treatment
• immune system phenotype
• abnormal spleen B cell follicle morphology (MGI Ref ID J:60223)
  • spleens from sixth generation mutants (but not earlier generations) show fewer follicles
• decreased spleen germinal center number (MGI Ref ID J:60223)
  • fifth and sixth generation homozygotes show a reduction in germinal centers following antigen (KLH) immunization
• decreased B cell proliferation (MGI Ref ID J:60223)
  • splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• decreased T cell proliferation (MGI Ref ID J:60223)
  • splenocytes (from both non-immunized and immunized) from sixth generation mutants show a decrease in the proliferative response to B and T cell mitogens
• increased B cell apoptosis (MGI Ref ID J:60223)
  • splenocytes from immunized fifth and sixth generation mice exhibit a small increase in apoptosis after mitogen treatment
• embryogenesis phenotype
• abnormal developmental patterning (MGI Ref ID J:53600)
  • a portion of embryos with open neural tube show absence of bilateral symmetry in the brain
• nervous system phenotype
• open neural tube (MGI Ref ID J:53600)
  • a percentage of embryos fail to close the neural tube, particularly in the forebrain and midbrain, at E10.5; penetrance of this defect increases with generation number, with 30% of fifth generation embryos showing an open neural tube
• reproductive system phenotype
• abnormal meiosis (MGI Ref ID J:89751)
  • chromosome pairing, synapsis, and recombination are severely impaired in meiocytes with irregular telomeres
• abnormal female meiosis (MGI Ref ID J:89751)
  • in response to telomere shortening, female germ cells arrest in early meiosis
  • meiocytes of fourth generation (G4) females with shortened telomeres bred with early generation males harboring relatively long telomeres, exhibit severely impaired chromosome pairing and synapsis and reduced meiotic recombination
  • synaptonemal complex protein 3 (SCP3) elements are altered in G4 female meiotic cells
• abnormal male meiosis (MGI Ref ID J:89751)
  • the number of spermatocytes with synaptonemal complex protein 3 (SCP3) lateral elements is decreased in the fourth generation (G4) homozygotes
• abnormal oocyte morphology (MGI Ref ID J:89751)
  • the number of oocytes that form synaptonemal complexes is decreased
• abnormal spermatocyte morphology (MGI Ref ID J:89751)
  • apoptosis is increased 5-fold in seminiferous tubules of G4 homozygotes; apoptosis is found in the outer layers of spermatocytes whereas the inner layer of spermatogonia remains intact
• decreased litter size (MGI Ref ID J:53600)
  • mutants of late generations show a decrease in litter size
• infertility (MGI Ref ID J:53600)
  • mutants are infertile at the sixth generation (of interbreeding) and infertile at the fourth generation of backcrossing to C57BL/6J
• male germ cell apoptosis (MGI Ref ID J:89751)
  • in response to telomere shortening, male germ cells undergo apoptosis
  • apoptotic depletion of germ cells in late generation mutants
• reduced female fertility (MGI Ref ID J:89751)
  • late generation pregnant females have fewer fetuses
• testicular atrophy (MGI Ref ID J:120065)
  • testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants
• behavior/neurological phenotype
• hypoactivity (MGI Ref ID J:110900)
  • older (6-8 months) fifth generation mutants often show a sudden decrease in activity
• growth/size phenotype
• decreased body size (MGI Ref ID J:120065)
  • late generation mutants have reduced body size and are fragile
• decreased body weight (MGI Ref ID J:120065)
  • late generation mutants have reduced body weight
• weight loss (MGI Ref ID J:110900)
  • older (6-8 months) fifth generation mutants often show sudden losses in body weight
• reduced fetal size (MGI Ref ID J:89751)
  • 41% of homozygous fetuses from late generation pregnant females are reduced in size
• muscle phenotype
• abnormal cardiac muscle contractility (MGI Ref ID J:110900)
  • fifth generation, but not second generation, mutants exhibit a decrease in +dP/dt
• abnormal cardiac muscle relaxation (MGI Ref ID J:110900)
  • fifth generation mutants exhibit a decrease in -dP/dt
• abnormal fetal cardiomyocyte proliferation (MGI Ref ID J:110900)
  • second and fifth generation mutants exhibit decreased cardiac myocyte proliferation
• abnormal myocardial fiber morphology (MGI Ref ID J:110900)
  • the volume of binucleated cardiomyocytes is increased by 24% in second generation mutants and 52% in fifth generation mutants
  • the volume of mononucleated cardiomyocytes is increased by 39% and 43% in second and fifth generation mutants, respectively
• decreased myocardial fiber number (MGI Ref ID J:110900)
  • cardiomyocyte number is decreased 16% and 49% in second and fifth generation mutants, respectively
• increased cardiomyocyte apoptosis (MGI Ref ID J:110900)
  • fifth generation mutants exhibit a 63% increase in cardiomyocyte apoptosis
• dilated cardiomyopathy (MGI Ref ID J:110900)
  • dilated cardiomyopathy develops in fifth generation mutants
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:96945)
  • homozygotes exhibit normal wound healing
• digestive/alimentary phenotype
• abnormal intestine morphology (MGI Ref ID J:120065)
  • the GI crypts of late generation mutants exhibit high levels of apoptosis
• endocrine/exocrine gland phenotype
• testicular atrophy (MGI Ref ID J:120065)
  • testicular atrophy and associated apoptotic depletion of germ cells in late generation mutants
• skeleton phenotype
• kyphosis (MGI Ref ID J:120065)
  • late generation mutants exhibit kyphosis
• skin/coat/nails phenotype
• alopecia (MGI Ref ID J:120065)
  • late generation mutants exhibit alopecia

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Terc^tm1Rdp related

Cancer Research
Genes Regulating Growth and Proliferation
Other (DNA Repair)
Tumor Suppressor Genes

Cell Biology Research
DNA Damage Response

Research Tools
Cell Biology Research
Genetics Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Terctm1Rdp
Allele Name		targeted mutation 1, Ronald DePinho
Allele Type		Targeted (knock-out)
Common Name(s)		TR-; Terc-; mTR-; mTerc-;
Mutation Made By		Carol Greider,   Johns Hopkins Univ School of Medicine
Strain of Origin		STOCK 129/Sv and C57BL/6J and SJL
ES Cell Line Name		WW6
ES Cell Line Strain		STOCK 129/Sv and C57BL/6J and SJL
Gene Symbol and Name		Terc, telomerase RNA component
Chromosome		3
Gene Common Name(s)		SCARNA19; TR; TRC3; hTR; mTER; mTR;
Molecular Note		Replacement of the entire gene with a neomycin cassette. [MGI Ref ID J:43517]

Genotyping

Genotyping Information

Genotyping Protocols

Terc^tm1Rdp, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Blasco MA; Lee HW; Hande MP; Samper E; Lansdorp PM; DePinho RA ; Greider CW. 1997. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [see comments] Cell 91(1):25-34. [PubMed: 9335332]  [MGI Ref ID J:43517]

Additional References

Herrera E; Samper E; Blasco MA. 1999. Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. EMBO J 18(5):1172-81. [PubMed: 10064584]  [MGI Ref ID J:53600]

Terc^tm1Rdp related

Akbay EA; Contreras CM; Perera SA; Sullivan JP; Broaddus RR; Schorge JO; Ashfaq R; Saboorian H; Wong KK; Castrillon DH. 2008. Differential roles of telomere attrition in type I and II endometrial carcinogenesis. Am J Pathol 173(2):536-44. [PubMed: 18599611]  [MGI Ref ID J:138286]

Allsopp RC; Morin GB; DePinho R; Harley CB; Weissman IL. 2003. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood 102(2):517-20. [PubMed: 12663456]  [MGI Ref ID J:115695]

Argilla D; Chin K; Singh M; Hodgson JG; Bosenberg M; de Solorzano CO; Lockett S; DePinho RA; Gray J; Hanahan D. 2004. Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes. Cancer Cell 6(4):373-85. [PubMed: 15488760]  [MGI Ref ID J:94774]

Artandi SE; Chang S; Lee SL; Alson S; Gottlieb GJ; Chin L; DePinho RA. 2000. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice [see comments] Nature 406(6796):641-5. [PubMed: 10949306]  [MGI Ref ID J:63843]

Autexier C. 2008. POT of gold: modeling dyskeratosis congenita in the mouse. Genes Dev 22(13):1731-6. [PubMed: 18593874]  [MGI Ref ID J:137424]

Benetti R; Garcia-Cao M; Blasco MA. 2007. Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet 39(2):243-50. [PubMed: 17237781]  [MGI Ref ID J:118330]

Blanco R; Munoz P; Flores JM; Klatt P; Blasco MA. 2007. Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis. Genes Dev 21(2):206-20. [PubMed: 17234886]  [MGI Ref ID J:117418]

Cayuela ML; Flores JM; Blasco MA. 2005. The telomerase RNA component Terc is required for the tumour-promoting effects of Tert overexpression. EMBO Rep 6(3):268-74. [PubMed: 15731767]  [MGI Ref ID J:96945]

Chang S. 2005. Modeling aging and cancer in the telomerase knockout mouse. Mutat Res 576(1-2):39-53. [PubMed: 15927211]  [MGI Ref ID J:99987]

Chang S; Multani AS; Cabrera NG; Naylor ML; Laud P; Lombard D; Pathak S; Guarente L; DePinho RA. 2004. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet 36(8):877-82. [PubMed: 15235603]  [MGI Ref ID J:91715]

Chiang YJ; Hemann MT; Hathcock KS; Tessarollo L; Feigenbaum L; Hahn WC; Hodes RJ. 2004. Expression of telomerase RNA template, but not telomerase reverse transcriptase, is limiting for telomere length maintenance in vivo. Mol Cell Biol 24(16):7024-31. [PubMed: 15282303]  [MGI Ref ID J:92243]

Chin L; Artandi SE; Shen Q; Tam A; Lee SL; Gottlieb GJ; Greider CW; DePinho RA. 1999. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97(4):527-38. [PubMed: 10338216]  [MGI Ref ID J:54988]

Choudhury AR; Ju Z; Djojosubroto MW; Schienke A; Lechel A; Schaetzlein S; Jiang H; Stepczynska A; Wang C; Buer J; Lee HW; von Zglinicki T; Ganser A; Schirmacher P; Nakauchi H; Rudolph KL. 2007. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet 39(1):99-105. [PubMed: 17143283]  [MGI Ref ID J:117492]

Du X; Shen J; Kugan N; Furth EE; Lombard DB; Cheung C; Pak S; Luo G; Pignolo RJ; DePinho RA; Guarente L; Johnson FB. 2004. Telomere shortening exposes functions for the mouse werner and bloom syndrome genes. Mol Cell Biol 24(19):8437-46. [PubMed: 15367665]  [MGI Ref ID J:93016]

Espejel S; Franco S; Rodriguez-Perales S; Bouffler SD; Cigudosa JC; Blasco MA. 2002. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. EMBO J 21(9):2207-19. [PubMed: 11980718]  [MGI Ref ID J:76498]

Espejel S; Franco S; Sgura A; Gae D; Bailey SM; Taccioli GE; Blasco MA. 2002. Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. EMBO J 21(22):6275-87. [PubMed: 12426399]  [MGI Ref ID J:111398]

Espejel S; Klatt P; Menissier-de Murcia J; Martin-Caballero J; Flores JM; Taccioli G; de Murcia G; Blasco MA. 2004. Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs. J Cell Biol 167(4):627-38. [PubMed: 15545322]  [MGI Ref ID J:94117]

Farazi PA; Glickman J; Jiang S; Yu A; Rudolph KL; DePinho RA. 2003. Differential impact of telomere dysfunction on initiation and progression of hepatocellular carcinoma. Cancer Res 63(16):5021-7. [PubMed: 12941829]  [MGI Ref ID J:85141]

Feldser D; Strong MA; Greider CW. 2006. Ataxia telangiectasia mutated (Atm) is not required for telomerase-mediated elongation of short telomeres. Proc Natl Acad Sci U S A 103(7):2249-51. [PubMed: 16467146]  [MGI Ref ID J:106070]

Feldser DM; Greider CW. 2007. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell 11(5):461-9. [PubMed: 17433785]  [MGI Ref ID J:121351]

Ferron S; Mira H; Franco S; Cano-Jaimez M; Bellmunt E; Ramirez C; Farinas I; Blasco MA. 2004. Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development 131(16):4059-70. [PubMed: 15269166]  [MGI Ref ID J:92059]

Flores I; Canela A; Vera E; Tejera A; Cotsarelis G; Blasco MA. 2008. The longest telomeres: a general signature of adult stem cell compartments. Genes Dev 22(5):654-67. [PubMed: 18283121]  [MGI Ref ID J:131719]

Flores I; Cayuela ML; Blasco MA. 2005. Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309(5738):1253-6. [PubMed: 16037417]  [MGI Ref ID J:100470]

Flores I; Evan G; Blasco MA. 2006. Genetic analysis of myc and telomerase interactions in vivo. Mol Cell Biol 26(16):6130-8. [PubMed: 16880523]  [MGI Ref ID J:111405]

Franco S; Alsheimer M; Herrera E; Benavente R; Blasco MA. 2002. Mammalian meiotic telomeres: composition and ultrastructure in telomerase-deficient mice. Eur J Cell Biol 81(6):335-40. [PubMed: 12113474]  [MGI Ref ID J:102812]

Franco S; Canela A; Klatt P; Blasco MA. 2005. Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models. Carcinogenesis 26(9):1613-26. [PubMed: 15860505]  [MGI Ref ID J:100743]

Franco S; Segura I; Riese HH; Blasco MA. 2002. Decreased B16F10 melanoma growth and impaired vascularization in telomerase-deficient mice with critically short telomeres. Cancer Res 62(2):552-9. [PubMed: 11809709]  [MGI Ref ID J:74001]

Franco S; van de Vrugt HJ; Fernandez P; Aracil M; Arwert F; Blasco MA. 2004. Telomere dynamics in Fancg-deficient mouse and human cells. Blood 104(13):3927-35. [PubMed: 15319283]  [MGI Ref ID J:95292]

Garcia-Cao I; Garcia-Cao M; Tomas-Loba A; Martin-Caballero J; Flores JM; Klatt P; Blasco MA; Serrano M. 2006. Increased p53 activity does not accelerate telomere-driven ageing. EMBO Rep 7(5):546-52. [PubMed: 16582880]  [MGI Ref ID J:116879]

Gonzalez-Suarez E; Goytisolo FA; Flores JM; Blasco MA. 2003. Telomere dysfunction results in enhanced organismal sensitivity to the alkylating agent N-methyl-N-nitrosourea. Cancer Res 63(21):7047-50. [PubMed: 14612493]  [MGI Ref ID J:87029]

Gonzalez-Suarez E; Samper E; Flores JM; Blasco MA. 2000. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis Nat Genet 26(1):114-7. [PubMed: 10973262]  [MGI Ref ID J:64363]

Greenberg RA; Chin L; Femino A; Lee KH; Gottlieb GJ; Singer RH; Greider CW; DePinho RA. 1999. Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell 97(4):515-25. [PubMed: 10338215]  [MGI Ref ID J:54989]

Gu BW; Bessler M; Mason PJ. 2008. A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage response independent of telomere length in mice. Proc Natl Acad Sci U S A 105(29):10173-8. [PubMed: 18626023]  [MGI Ref ID J:138335]

Hande MP; Samper E; Lansdorp P; Blasco MA. 1999. Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. J Cell Biol 144(4):589-601. [PubMed: 10037783]  [MGI Ref ID J:53241]

Hao LY; Armanios M; Strong MA; Karim B; Feldser DM; Huso D; Greider CW. 2005. Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell 123(6):1121-31. [PubMed: 16360040]  [MGI Ref ID J:115778]

Hao LY; Greider CW. 2004. Genomic instability in both wild-type and telomerase null MEFs. Chromosoma 113(2):62-8. [PubMed: 15258806]  [MGI Ref ID J:103501]

Hao LY; Strong MA; Greider CW. 2004. Phosphorylation of H2AX at short telomeres in T cells and fibroblasts. J Biol Chem 279(43):45148-54. [PubMed: 15322096]  [MGI Ref ID J:93974]

Hathcock KS; Hemann MT; Opperman KK; Strong MA; Greider CW; Hodes RJ. 2002. Haploinsufficiency of mTR results in defects in telomere elongation. Proc Natl Acad Sci U S A 99(6):3591-6. [PubMed: 11904421]  [MGI Ref ID J:81782]

Hemann MT; Greider CW. 1999. G-strand overhangs on telomeres in telomerase-deficient mouse cells. Nucleic Acids Res 27(20):3964-9. [PubMed: 10497259]  [MGI Ref ID J:58129]

Hemann MT; Strong MA; Hao LY; Greider CW. 2001. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107(1):67-77. [PubMed: 11595186]  [MGI Ref ID J:107711]

Herrera E; Martinez-A C; Blasco MA. 2000. Impaired germinal center reaction in mice with short telomeres. EMBO J 19(3):472-81. [PubMed: 10654945]  [MGI Ref ID J:60223]

Herrera E; Samper E; Blasco MA. 1999. Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. EMBO J 18(5):1172-81. [PubMed: 10064584]  [MGI Ref ID J:53600]

Herrera E; Samper E; Martin-Caballero J; Flores JM; Lee HW; Blasco MA. 1999. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J 18(11):2950-60. [PubMed: 10357808]  [MGI Ref ID J:55545]

Hockemeyer D; Daniels JP; Takai H; de Lange T. 2006. Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres. Cell 126(1):63-77. [PubMed: 16839877]  [MGI Ref ID J:112185]

Hockemeyer D; Palm W; Wang RC; Couto SS; de Lange T. 2008. Engineered telomere degradation models dyskeratosis congenita. Genes Dev 22(13):1773-85. [PubMed: 18550783]  [MGI Ref ID J:137372]

Jiang H; Schiffer E; Song Z; Wang J; Zurbig P; Thedieck K; Moes S; Bantel H; Saal N; Jantos J; Brecht M; Jeno P; Hall MN; Hager K; Manns MP; Hecker H; Ganser A; Dohner K; Bartke A; Meissner C; Mischak H; Ju Z; Rudolph KL. 2008. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci U S A 105(32):11299-304. [PubMed: 18695223]  [MGI Ref ID J:140477]

Ju Z; Jiang H; Jaworski M; Rathinam C; Gompf A; Klein C; Trumpp A; Rudolph KL. 2007. Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat Med 13(6):742-7. [PubMed: 17486088]  [MGI Ref ID J:121891]

Karlseder J; Kachatrian L; Takai H; Mercer K; Hingorani S; Jacks T; de Lange T. 2003. Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol Cell Biol 23(18):6533-41. [PubMed: 12944479]  [MGI Ref ID J:85440]

Khoo CM; Carrasco DR; Bosenberg MW; Paik JH; Depinho RA. 2007. Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse. Proc Natl Acad Sci U S A 104(10):3931-6. [PubMed: 17360455]  [MGI Ref ID J:120065]

Laud PR; Multani AS; Bailey SM; Wu L; Ma J; Kingsley C; Lebel M; Pathak S; DePinho RA; Chang S. 2005. Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev 19(21):2560-70. [PubMed: 16264192]  [MGI Ref ID J:102524]

Lechel A; Holstege H; Begus Y; Schienke A; Kamino K; Lehmann U; Kubicka S; Schirmacher P; Jonkers J; Rudolph KL. 2007. Telomerase deletion limits progression of p53-mutant hepatocellular carcinoma with short telomeres in chronic liver disease. Gastroenterology 132(4):1465-75. [PubMed: 17433324]  [MGI Ref ID J:128326]

Lee HW; Blasco MA; Gottlieb GJ; Horner JW 2nd; Greider CW; DePinho RA. 1998. Essential role of mouse telomerase in highly proliferative organs. Nature 392(6676):569-74. [PubMed: 9560153]  [MGI Ref ID J:46933]

Lee J; Sung YH; Cheong C; Choi YS; Jeon HK; Sun W; Hahn WC; Ishikawa F; Lee HW. 2008. TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene 27(26):3754-60. [PubMed: 18223679]  [MGI Ref ID J:138281]

Leri A; Franco S; Zacheo A; Barlucchi L; Chimenti S; Limana F; Nadal-Ginard B; Kajstura J; Anversa P; Blasco MA. 2003. Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J 22(1):131-9. [PubMed: 12505991]  [MGI Ref ID J:110900]

Liu L; Blasco M; Trimarchi J; Keefe D. 2002. An Essential Role for Functional Telomeres in Mouse Germ Cells during Fertilization and Early Development. Dev Biol 249(1):74. [PubMed: 12217319]  [MGI Ref ID J:78765]

Liu L; Blasco MA; Keefe DL. 2002. Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles. EMBO Rep 3(3):230-4. [PubMed: 11882542]  [MGI Ref ID J:108982]

Liu L; DiGirolamo CM; Navarro PA; Blasco MA; Keefe DL. 2004. Telomerase deficiency impairs differentiation of mesenchymal stem cells. Exp Cell Res 294(1):1-8. [PubMed: 14980495]  [MGI Ref ID J:115468]

Liu L; Franco S; Spyropoulos B; Moens PB; Blasco MA; Keefe DL. 2004. Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci U S A 101(17):6496-501. [PubMed: 15084742]  [MGI Ref ID J:89751]

Maser RS; Choudhury B; Campbell PJ; Feng B; Wong KK; Protopopov A; O'Neil J; Gutierrez A; Ivanova E; Perna I; Lin E; Mani V; Jiang S; McNamara K; Zaghlul S; Edkins S; Stevens C; Brennan C; Martin ES; Wiedemeyer R; Kabbarah O; Nogueira C; Histen G; Aster J; Mansour M; Duke V; Foroni L; Fielding AK; Goldstone AH; Rowe JM; Wang YA; Look AT; Stratton MR; Chin L; Futreal PA; DePinho RA. 2007. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 447(7147):966-71. [PubMed: 17515920]  [MGI Ref ID J:122751]

Maser RS; Wong KK; Sahin E; Xia H; Naylor M; Hedberg HM; Artandi SE; DePinho RA. 2007. DNA-dependent protein kinase catalytic subunit is not required for dysfunctional telomere fusion and checkpoint response in the telomerase-deficient mouse. Mol Cell Biol 27(6):2253-65. [PubMed: 17145779]  [MGI Ref ID J:118902]

Munoz P; Blanco R; Flores JM; Blasco MA. 2005. XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet 37(10):1063-71. [PubMed: 16142233]  [MGI Ref ID J:102653]

Perera SA; Maser RS; Xia H; McNamara K; Protopopov A; Chen L; Hezel AF; Kim CF; Bronson RT; Castrillon DH; Chin L; Bardeesy N; Depinho RA; Wong KK. 2008. Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis 29(4):747-53. [PubMed: 18283039]  [MGI Ref ID J:133322]

Perez-Rivero G; Ruiz-Torres MP; Rivas-Elena JV; Jerkic M; Diez-Marques ML; Lopez-Novoa JM; Blasco MA; Rodriguez-Puyol D. 2006. Mice deficient in telomerase activity develop hypertension because of an excess of endothelin production. Circulation 114(4):309-17. [PubMed: 16831983]  [MGI Ref ID J:123085]

Poch E; Carbonell P; Franco S; Diez-Juan A; Blasco MA; Andres V. 2004. Short telomeres protect from diet-induced atherosclerosis in apolipoprotein E-null mice. FASEB J 18(2):418-20. [PubMed: 14688198]  [MGI Ref ID J:119421]

Qi L; Strong MA; Karim BO; Armanios M; Huso DL; Greider CW. 2003. Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis. Cancer Res 63(23):8188-96. [PubMed: 14678974]  [MGI Ref ID J:87091]

Qi L; Strong MA; Karim BO; Huso DL; Greider CW. 2005. Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour formation. Nat Cell Biol 7(7):706-11. [PubMed: 15965466]  [MGI Ref ID J:100156]

Rodriguez S; Goyanes V; Segrelles E; Blasco M; Gosalvez J; Fernandez JL. 2005. Critically short telomeres are associated with sperm DNA fragmentation. Fertil Steril 84(4):843-5. [PubMed: 16213831]  [MGI Ref ID J:106586]

Rudolph KL; Chang S; Lee HW; Blasco M; Gottlieb GJ; Greider C; DePinho RA. 1999. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96(5):701-12. [PubMed: 10089885]  [MGI Ref ID J:53350]

Rudolph KL; Chang S; Millard M; Schreiber-Agus N; DePinho RA. 2000. Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery [see comments] Science 287(5456):1253-8. [PubMed: 10678830]  [MGI Ref ID J:60636]

Rudolph KL; Millard M; Bosenberg MW; DePinho RA. 2001. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28(2):155-9. [PubMed: 11381263]  [MGI Ref ID J:69730]

Satyanarayana A; Wiemann SU; Buer J; Lauber J; Dittmar KE; Wustefeld T; Blasco MA; Manns MP; Rudolph KL. 2003. Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells. EMBO J 22(15):4003-13. [PubMed: 12881434]  [MGI Ref ID J:84928]

Schaetzlein S; Kodandaramireddy NR; Ju Z; Lechel A; Stepczynska A; Lilli DR; Clark AB; Rudolph C; Kuhnel F; Wei K; Schlegelberger B; Schirmacher P; Kunkel TA; Greenberg RA; Edelmann W; Rudolph KL. 2007. Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice. Cell 130(5):863-77. [PubMed: 17803909]  [MGI Ref ID J:129929]

Schaetzlein S; Lucas-Hahn A; Lemme E; Kues WA; Dorsch M; Manns MP; Niemann H; Rudolph KL. 2004. Telomere length is reset during early mammalian embryogenesis. Proc Natl Acad Sci U S A 101(21):8034-8. [PubMed: 15148368]  [MGI Ref ID J:90665]

Schoeftner S; Blasco MA. 2008. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10(2):228-36. [PubMed: 18157120]  [MGI Ref ID J:132362]

Siegl-Cachedenier I; Munoz P; Flores JM; Klatt P; Blasco MA. 2007. Deficient mismatch repair improves organismal fitness and survival of mice with dysfunctional telomeres. Genes Dev 21(17):2234-47. [PubMed: 17785530]  [MGI Ref ID J:125218]

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Wiemann SU; Satyanarayana A; Buer J; Kamino K; Manns MP; Rudolph KL. 2005. Contrasting effects of telomere shortening on organ homeostasis, tumor suppression, and survival during chronic liver damage. Oncogene 24(9):1501-9. [PubMed: 15608677]  [MGI Ref ID J:96885]

Wong KK; Chang S; Weiler SR; Ganesan S; Chaudhuri J; Zhu C; Artandi SE; Rudolph KL; Gottlieb GJ; Chin L; Alt FW; DePinho RA. 2000. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation Nat Genet 26(1):85-8. [PubMed: 10973255]  [MGI Ref ID J:64366]

Wong KK; Maser RS; Bachoo RM; Menon J; Carrasco DR; Gu Y; Alt FW; DePinho RA. 2003. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 421(6923):643-8. [PubMed: 12540856]  [MGI Ref ID J:81552]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a mixed background and has been backcrossed to C57BL/6J for at least seven generations. Coat color expected from breeding:Black
Mating System	Heterozygote x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.