Strain Name:

FVB.Cg-Krt8tm1Rgo/J

Stock Number:

007031

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator M. Bishr Omary,   Stanford University & Palo Alto VA Medic

Description
Homozygous mutants display an incompletely penetrant, reduced viability that is genetic background dependent. On this FVB congenic background, approximately half of homozygous mutant pups die during embryonic development due to placental insufficiency. Maternal TNF (tumor necrosis factor) and TNFR2 (TNFRSF1B, tumor necrosis factor receptor superfamily, member 1b) influence survival of null embyos. Surviving homozygous females have markedly reduced productivity, but males are fertile. Homozygous adult mice develop inflammatory bowel disease, diarrhea, and colorectal hyperplasia with occasional anorectal prolapse. Lesions affect the cecum, remaining colon and rectum, but only minimally affect the small intestine. Elongation of the colonic crypts is accompanied by an inflammation of the lamina propria and submucosa. Livers from homozygous mutant mice display mild injury under basal conditions but a very high sensitivity to toxins and apoptotic stimuli. Minor liver and intestinal sensitivity have been reported in heterozygotes. This strain may be useful as model of inflammatory bowel disease or for its predisposition to liver injury. Other glandular organs in these mice may be useful subjects for study.

Development
A targeting vector was designed to replace most of the first exon, including the ATG translation initiation codon, with a neomycin resistance cassette. The linearized vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. C57BL/6 and 129 mixed background animals were backcrossed at least six times to FVB/N prior to arrival at The Jackson Laboratory.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Krt8
017947   STOCK Tg(Krt8-cre/ERT2)17Blpn/J
View Strains carrying other alleles of Krt8     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Krt8tm1Rgo/Krt8tm1Rgo

        involves: 129S2/SvPas * C57BL/6
  • mortality/aging
  • partial embryonic lethality during organogenesis
    • normal survival through E9.5   (MGI Ref ID J:12899)
    • dramatically reduced survival between E12 and E13   (MGI Ref ID J:12899)
    • small proportion of homozygotes (6%) survive to adulthood on this background   (MGI Ref ID J:12899)
    • tetraploid rescue of embryonic lethality   (MGI Ref ID J:121811)
  • embryogenesis phenotype
  • abnormal extraembryonic tissue physiology
    • massive hemorrhage of maternal blood between the deciduas capsularis and the parietal yolk sac   (MGI Ref ID J:121811)
    • impaired placental function   (MGI Ref ID J:121811)
  • abnormal placenta morphology
    • partially coagulated blood accumulates between the decidua and the yolk sac   (MGI Ref ID J:121811)
    • abnormal trophoblast layer morphology
      • disruption of the trophoblast giant cell layer   (MGI Ref ID J:121811)
      • abnormal trophoblast giant cells
        • degeneration of trophoblast giant cells   (MGI Ref ID J:121811)
  • decreased embryo weight
    • 65-70% of normal weight by E12.5   (MGI Ref ID J:12899)
  • cardiovascular system phenotype
  • internal hemorrhage
    • internal bleeding observed in some embryos   (MGI Ref ID J:12899)
  • hematopoietic system phenotype
  • extramedullary hematopoiesis
    • abnormal accumulations of nucleated embryonic erythrocytes in the liver at E12.5   (MGI Ref ID J:12899)
  • reproductive system phenotype
  • reduced female fertility
    • reduced female fertility   (MGI Ref ID J:12899)
  • growth/size/body phenotype
  • decreased embryo weight
    • 65-70% of normal weight by E12.5   (MGI Ref ID J:12899)

Krt8tm1Rgo/Krt8tm1Rgo

        involves: 129S2/SvPas * C57BL/6 * FVB/N
  • mortality/aging
  • partial embryonic lethality during organogenesis
    • 36% of homozygotes survive to adulthood after one backcross to FVB/N   (MGI Ref ID J:22116)
    • 55% of homozygotes survive to adulthood after two or more backcrosses to FVB/N   (MGI Ref ID J:22116)
  • digestive/alimentary phenotype
  • abnormal colon morphology
    • hyperplastic lesions in the colon and rectum   (MGI Ref ID J:22116)
    • elongated villi   (MGI Ref ID J:22116)
    • frequent mitotic colonocytes   (MGI Ref ID J:89299)
    • colonocyte sloughing into the lumen in some areas   (MGI Ref ID J:89299)
  • abnormal intestinal epithelium morphology
    • mistargeting of apical membrane proteins in the epithelium of the small intestine   (MGI Ref ID J:118021)
  • abnormal intestinal mineral absorption
    • decreased net sodium absorption   (MGI Ref ID J:89299)
    • significantly decreased net chloride flux resulting in net chloride secretion   (MGI Ref ID J:89299)
  • diarrhea
    • watery stools   (MGI Ref ID J:89299)
  • rectal prolapse
    • anorectal prolapse developing between 9 weeks and 1 year of age   (MGI Ref ID J:22116)
  • hematopoietic system phenotype
  • enlarged spleen
    • moderate splenomegaly   (MGI Ref ID J:22116)
  • liver/biliary system phenotype
  • abnormal hepatocyte morphology   (MGI Ref ID J:121814)
    • nucleus of hepatocytes often displaced to the periphery of the cell when on a lithogenic diet   (MGI Ref ID J:86719)
    • reduced viability of hepatocytes isolated by collagenase perfusion compared to wild-type   (MGI Ref ID J:44938)
    • liver lesions, necrosis and abnormal hepatocyte cell cycle correlating with multinuclear cells and abnormal hepatocellular architecture   (MGI Ref ID J:106541)
    • increased sensitivity to liver toxins   (MGI Ref ID J:121815)
    • increased sensitivity of hepatocytes to apoptosis (J:121814)   (MGI Ref ID J:121813)
  • hepatic necrosis   (MGI Ref ID J:22116)
  • hepatic steatosis
    • liver steatosis develops on a lithogenic diet   (MGI Ref ID J:86719)
  • liver hemorrhage
    • increased hemorrhage seen in the liver on a lithogenic diet   (MGI Ref ID J:86719)
  • cardiovascular system phenotype
  • liver hemorrhage
    • increased hemorrhage seen in the liver on a lithogenic diet   (MGI Ref ID J:86719)
  • immune system phenotype
  • chronic inflammation
    • increased inflammation on a lithogenic diet   (MGI Ref ID J:86719)
    • Th-2 mediated inflammation of the colon   (MGI Ref ID J:98058)
  • enlarged spleen
    • moderate splenomegaly   (MGI Ref ID J:22116)
  • reproductive system phenotype
  • female infertility
    • females are sterile but males are normally fertile   (MGI Ref ID J:22116)
  • growth/size/body phenotype
  • decreased body weight   (MGI Ref ID J:89299)
View Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)

Immunology, Inflammation and Autoimmunity Research
Inflammation
      Inflammatory bowel disease

Research Tools
Toxicology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Krt8tm1Rgo
Allele Name targeted mutation 1, Robert G Oshima
Allele Type Targeted (Null/Knockout)
Common Name(s) K8-; mK8 -;
Mutation Made By Diana Toivola,   Stanford University
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Krt8, keratin 8
Chromosome 15
Gene Common Name(s) AA960620; AL022697; AU019895; CARD2; CK-8; CK8; CYK8; CYKER; EndoA; K2C8; K8; KO; Krt-2.8; Krt2-8; cytokeratin 8; cytokeratin-8; cytokeratin8; expressed sequence AA960620; expressed sequence AL022697; expressed sequence AU019895; keratin complex 2, basic, gene 8; keratin gene complex 2, gene 8;
Molecular Note A neomycin resistance cassette replaced a DNA segment containing most of the first exon including the translation initiation codon. Northern blot analysis on RNA isolated from gut, liver, kidney and spleen demonstrated that an aberrant transcript was made in gut, but no transcript was detectable elsewhere. Immunohistochemistry on sections of intestine of homozygous mice confirmed that no detectable protein was expressed from this allele. [MGI Ref ID J:12899]

Genotyping

Genotyping Information

Genotyping Protocols

Krt8tm1Rgoalternate1,

Separated MCA


Krt8tm1Rgoalternate1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Baribault H; Penner J; Iozzo RV; Wilson-Heiner M. 1994. Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev 8(24):2964-73. [PubMed: 7528156]  [MGI Ref ID J:22116]

Baribault H; Price J; Miyai K; Oshima RG. 1993. Mid-gestational lethality in mice lacking keratin 8. Genes Dev 7(7A):1191-202. [PubMed: 7686525]  [MGI Ref ID J:12899]

Additional References

Krt8tm1Rgo related

Alam CM; Silvander JS; Daniel EN; Tao GZ; Kvarnstrom SM; Alam P; Omary MB; Hanninen A; Toivola DM. 2013. Keratin 8 modulates beta-cell stress responses and normoglycaemia. J Cell Sci 126(Pt 24):5635-44. [PubMed: 24144696]  [MGI Ref ID J:211906]

Ameen NA; Figueroa Y; Salas PJ. 2001. Anomalous apical plasma membrane phenotype in CK8-deficient mice indicates a novel role for intermediate filaments in the polarization of simple epithelia. J Cell Sci 114(Pt 3):563-75. [PubMed: 11171325]  [MGI Ref ID J:118021]

Caulin C; Ware CF; Magin TM; Oshima RG. 2000. Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. J Cell Biol 149(1):17-22. [PubMed: 10747083]  [MGI Ref ID J:121814]

Gilbert S; Loranger A; Daigle N; Marceau N. 2001. Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. J Cell Biol 154(4):763-73. [PubMed: 11514590]  [MGI Ref ID J:121813]

Habtezion A; Toivola DM; Asghar MN; Kronmal GS; Brooks JD; Butcher EC; Omary MB. 2011. Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon. Proc Natl Acad Sci U S A 108(4):1445-50. [PubMed: 21220329]  [MGI Ref ID J:168244]

Habtezion A; Toivola DM; Butcher EC; Omary MB. 2005. Keratin-8-deficient mice develop chronic spontaneous Th2 colitis amenable to antibiotic treatment. J Cell Sci 118(Pt 9):1971-80. [PubMed: 15840656]  [MGI Ref ID J:98058]

Haybaeck J; Stumptner C; Thueringer A; Kolbe T; Magin TM; Hesse M; Fickert P; Tsybrovskyy O; Muller H; Trauner M; Zatloukal K; Denk H. 2012. Genetic background effects of keratin 8 and 18 in a DDC-induced hepatotoxicity and Mallory-Denk body formation mouse model. Lab Invest 92(6):857-67. [PubMed: 22449798]  [MGI Ref ID J:184713]

Jaquemar D; Kupriyanov S; Wankell M; Avis J; Benirschke K; Baribault H; Oshima RG. 2003. Keratin 8 protection of placental barrier function. J Cell Biol 161(4):749-56. [PubMed: 12771125]  [MGI Ref ID J:121811]

Ku NO; Omary MB. 2006. A disease- and phosphorylation-related nonmechanical function for keratin 8. J Cell Biol 174(1):115-25. [PubMed: 16818723]  [MGI Ref ID J:111195]

Lee J; Jang KH; Kim H; Lim Y; Kim S; Yoon HN; Chung IK; Roth J; Ku NO. 2013. Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-kappaB and SAPKs but not decreased c-Flip. Biol Open 2(7):695-702. [PubMed: 23862017]  [MGI Ref ID J:199436]

Loranger A; Duclos S; Grenier A; Price J; Wilson-Heiner M; Baribault H; Marceau N. 1997. Simple epithelium keratins are required for maintenance of hepatocyte integrity. Am J Pathol 151(6):1673-83. [PubMed: 9403718]  [MGI Ref ID J:44938]

Mathew J; Galarneau L; Loranger A; Gilbert S; Marceau N. 2008. Keratin-protein kinase C interaction in reactive oxygen species-induced hepatic cell death through mitochondrial signaling. Free Radic Biol Med 45(4):413-24. [PubMed: 18486629]  [MGI Ref ID J:137796]

Odaka C; Loranger A; Takizawa K; Ouellet M; Tremblay MJ; Murata S; Inoko A; Inagaki M; Marceau N. 2013. Keratin 8 is required for the maintenance of architectural structure in thymus epithelium. PLoS One 8(9):e75101. [PubMed: 24086449]  [MGI Ref ID J:207745]

Tamai Y; Ishikawa To; Bosl MR; Mori M; Nozaki M; Baribault H; Oshima RG; Taketo MM. 2000. Cytokeratins 8 and 19 in the mouse placental development J Cell Biol 151(3):563-72. [PubMed: 11062258]  [MGI Ref ID J:65498]

Tao GZ; Looi KS; Toivola DM; Strnad P; Zhou Q; Liao J; Wei Y; Habtezion A; Omary MB. 2009. Keratins modulate the shape and function of hepatocyte mitochondria: a mechanism for protection from apoptosis. J Cell Sci 122(Pt 21):3851-5. [PubMed: 19825937]  [MGI Ref ID J:154607]

Tao GZ; Toivola DM; Zhong B; Michie SA; Resurreccion EZ; Tamai Y; Taketo MM; Omary MB. 2003. Keratin-8 null mice have different gallbladder and liver susceptibility to lithogenic diet-induced injury. J Cell Sci 116(Pt 22):4629-38. [PubMed: 14576356]  [MGI Ref ID J:86719]

Toivola DM; Krishnan S; Binder HJ; Singh SK; Omary MB. 2004. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J Cell Biol 164(6):911-21. [PubMed: 15007064]  [MGI Ref ID J:89299]

Toivola DM; Nakamichi I; Strnad P; Michie SA; Ghori N; Harada M; Zeh K; Oshima RG; Baribault H; Omary MB. 2008. Keratin Overexpression Levels Correlate with the Extent of Spontaneous Pancreatic Injury. Am J Pathol 172(4):882-892. [PubMed: 18349119]  [MGI Ref ID J:133347]

Toivola DM; Nieminen MI; Hesse M; He T; Baribault H; Magin TM; Omary MB; Eriksson JE. 2001. Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18. Hepatology 34(6):1174-83. [PubMed: 11732007]  [MGI Ref ID J:106541]

Toivola DM; Omary MB; Ku NO; Peltola O; Baribault H; Eriksson JE. 1998. Protein phosphatase inhibition in normal and keratin 8/18 assembly-incompetent mouse strains supports a functional role of keratin intermediate filaments in preserving hepatocyte integrity. Hepatology 28(1):116-28. [PubMed: 9657104]  [MGI Ref ID J:121815]

Zatloukal K; Stumptner C; Lehner M; Denk H; Baribault H; Eshkind LG; Franke WW. 2000. Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies. Am J Pathol 156(4):1263-74. [PubMed: 10751352]  [MGI Ref ID J:108262]

Zhong B; Omary MB. 2004. Actin overexpression parallels severity of pancreatic injury. Exp Cell Res 299(2):404-14. [PubMed: 15350539]  [MGI Ref ID J:92840]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, heterozygotes may be used as breeders. Homozygous females are considered to be "infertile", but homozygous males can breed.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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