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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?pN1 Generation Definitions   Donating Investigator Robert S Williams,   Duke University School of Medicine

Description
Mice homozygous for the Cycs^tm1Wlm targeted-mutant allele die in utero by embryonic day 10.5, but cell lines established from early Cycs-null embryos are viable under conditions that compensate for defective oxidative phosphorylation. Cells lacking cytochrome c show reduced caspase 3 activation, and are resistant to the proapoptotic effects of UV irradiation, serum withdrawal, and staurosporine. Cells lacking cytochrome c, however, do demonstrate an increased sensitivity to cell death signals triggered by tumor necrosis factor, alpha. Heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

Development
A targeting vector containing neomycin resistance and thymidine kinase genes was used to disrupt the entire gene and flanking sequences. The construct was electroporated into 129-derived KG-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric animals were crossed to C57BL/6 mice.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Thrombocytopenia 4; THC4   (CYCS)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Cycs^tm1Wlm/Cycs^tm1Wlm

        involves: 129X1/SvJ * C57BL/6

• mortality/aging
• complete embryonic lethality during organogenesis
  • homozygous null embryos died by midgestation; no viable embryos were found after E10.5   (MGI Ref ID J:62276)
• cellular phenotype
• abnormal apoptosis
  • mutant cells showed reduced caspase-3 activation; caspase-3 activating activity could be rescued by exogenous cytochrome c   (MGI Ref ID J:62276)
  • mutants cells were resistant to the proapoptotic effects of UV irradiation, serum withdrawal, or staurosporine   (MGI Ref ID J:62276)
  • mutants cells showed increased sensitivity to cell death signals triggered by TNF, both in the presence or absence of cycloheximide   (MGI Ref ID J:62276)
• abnormal cellular respiration
  • cells derived from E8.5 mutant embryos showed respiratory insufficiency and enhanced anaerobic glycolysis   (MGI Ref ID J:62276)
  • cell viability and proliferation improved by supplementing the medium with uridine and pyruvate   (MGI Ref ID J:62276)
• embryogenesis phenotype
• abnormal extraembryonic tissue morphology
  • at E9.5, mutant embryos were enclosed in a ball-like structure formed by the yolk sac and the amnion   (MGI Ref ID J:62276)
• decreased embryo size
  • by E8.5, homozygous null embryos had a strikingly reduced size   (MGI Ref ID J:62276)
• embryonic growth retardation
  • up to E9.5, development appeared to progress in a relatively normal but delayed manner   (MGI Ref ID J:62276)
  • at E9.5, mutant embryos displayed a primitive heart tube, somites and an allantois, features consistent with ~E8 in wild-type   (MGI Ref ID J:62276)
• growth/size phenotype
• decreased embryo size
  • by E8.5, homozygous null embryos had a strikingly reduced size   (MGI Ref ID J:62276)
• embryonic growth retardation
  • up to E9.5, development appeared to progress in a relatively normal but delayed manner   (MGI Ref ID J:62276)
  • at E9.5, mutant embryos displayed a primitive heart tube, somites and an allantois, features consistent with ~E8 in wild-type   (MGI Ref ID J:62276)

View Research Applications

Research Applications

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

Cycs^tm1Wlm related

Apoptosis Research
Death Receptors
Endogenous Regulators
Extracellular Modulators

Cancer Research
Genes Regulating Growth and Proliferation

Cardiovascular Research
Heart Abnormalities

Cell Biology Research
DNA Damage Response
Genes Regulating Growth and Proliferation

Developmental Biology Research
Embryonic Lethality (Homozygous)
Growth Defects

Research Tools
Apoptosis Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cycstm1Wlm
Allele Name		targeted mutation 1, Robert Sanders Williams
Allele Type		Targeted (knock-out)
Common Name(s)		Cyt c-;
Mutation Made By		Robert Williams,   Duke University School of Medicine
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		KG-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Cycs, cytochrome c, somatic
Chromosome		6
Gene Common Name(s)		CYCSA;
Molecular Note		A neomycin resistance cassette replaced the two protein coding exons. Immunoblot analysis did not detect endogenous protein in cells cultured from E8-E9 embryos of homozygous mutant mice. [MGI Ref ID J:62276]

Genotyping

Genotyping Information

Genotyping Protocols

Cycs^tm1Wlm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li K; Li Y; Shelton JM; Richardson JA; Spencer E; Chen ZJ; Wang X; Williams RS. 2000. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell 101(4):389-99. [PubMed: 10830166]  [MGI Ref ID J:62276]

Additional References

Cycs^tm1Wlm related

Mansfield KD; Guzy RD; Pan Y; Young RM; Cash TP; Schumacker PT; Simon MC. 2005. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1(6):393-9. [PubMed: 16054088]  [MGI Ref ID J:129813]

Vempati UD; Diaz F; Barrientos A; Narisawa S; Mian AM; Millan JL; Boise LH; Moraes CT. 2007. Role of cytochrome C in apoptosis: increased sensitivity to tumor necrosis factor alpha is associated with respiratory defects but not with lack of cytochrome C release. Mol Cell Biol 27(5):1771-83. [PubMed: 17210651]  [MGI Ref ID J:118859]

Vempati UD; Han X; Moraes CT. 2009. Lack of cytochrome c in mouse fibroblasts disrupts assembly/stability of respiratory complexes I and IV. J Biol Chem 284(7):4383-91. [PubMed: 19075019]  [MGI Ref ID J:147780]

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 & Husbandry	This strain originated on a B6;129 background. The donating investigator maintains this strain by mating heterozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
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 regarding Terms of Use

Contracts Administration

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

JAX^® Mice, Products & Services Conditions of Use

"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.

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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.