Description

Strain Information

Former Names B6;129X1-Mcl1tm3Sjk/J    (Changed: 17-JAN-07 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation ?+F1pN1   Donating Investigator Stanley Korsmeyer,   Dana-Farber Cancer Institute

Description
Mice that are homozygous for the targeted mutation are viable, normal in size, and do not display any gross physical or behavioral abnormalities. The donating investigator indicates that homozygous males have severely reduced fertility for unknown reasons, while females have normal fertility. Endogenous protein expression is unaffected by the inserted loxP sequences. When bred to mice with a cre recombinase gene under the control of a promoter of interest, exon 1 of the targeted gene is deleted in the tissue of interest. These mutant mice may be useful in studying global, temporal, or tissue-specific deletion of the endogenous gene, particularly in studies of immune function, including apoptosis, B and T cell development, and bone marrow cell differentiation.

When bred to a strain with the targeted null allele (Stock No. 006072) and a strain with a Cd19 null allele and expressing Cre recombinase during the B lymphocyte development (Stock No. 004126), this mutant mouse strain may be useful in studies of lymphocyte development.

When bred to a strain with the targeted null allele (Stock No. 006072) and a strain expressing interferon inducible Cre recombinase in the lymphocytes (Stock No. 003556), this mutant mouse strain may be useful in studies of lymphocyte development.

Development
A targeting vector was designed to insert a loxP site upstream of transcriptional start ATG of the endogenous gene. An additional targeting vector was then used to insert a loxP-flanked cytomegalovirus (CMV) promoter driving the expression of a hygromycin–thymidine kinase fusion protein (HYG-Tk) into intron 1 of the endogenous gene. This construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells and then transiently transfected with CMV-Cre. Cre-mediated recombination resulting in a loxP-flanked exon 1 (and deletion of the HYG-Tk) were selected and injected into C57BL/6 blastocysts. Chimeric mice were crossed to C57BL/6 and the resulting heterozygotes were intercrossed to generate homozygotes prior to arrival at The Jackson Laboratory. These mice were crossed with "B6129F1" mice for at least one generation after arriving at The Jackson Laboratory.

Related Strains

Strains carrying other alleles of Mcl1

006072

B6.129X1-Mcl1tm2Sjk/J

View Strains carrying other alleles of Mcl1     (1 strain)

Additional Web Information

Cre-lox Systems

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.

Mcl1^tm3Sjk/Mcl1^tm3Sjk

        involves: 129X1/SvJ

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:86906)
  • mice were viable and born at the expected Mendelian frequency

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Cd19^tm1(cre)Cgn/Cd19⁺ Mcl1^tm2Sjk/Mcl1^tm3Sjk

        involves: 129X1/SvJ   (conditional)

• hematopoietic system phenotype
• abnormal B cell differentiation (MGI Ref ID J:86906)
• absent early pro-B cells (MGI Ref ID J:86906)
• absent late pro-B cells (MGI Ref ID J:86906)
• absent pre-B cells (MGI Ref ID J:86906)
• arrested B cell differentiation (MGI Ref ID J:86906)
  • arrested at pro-B cell stage
• decreased B cell number (MGI Ref ID J:86906)
  • decrease in peripheral B cells
  • 88% reduction of splenic B cells relative to controls
  • near absence of lymph node B cells
  • detected peripheral B cells did not undergo cre-mediated recombination
• absent pre-B cells (MGI Ref ID J:86906)
• increased B cell apoptosis (MGI Ref ID J:86906)
  • increased apoptosis at pro-B cell stage
• immune system phenotype
• abnormal B cell differentiation (MGI Ref ID J:86906)
• absent early pro-B cells (MGI Ref ID J:86906)
• absent late pro-B cells (MGI Ref ID J:86906)
• absent pre-B cells (MGI Ref ID J:86906)
• arrested B cell differentiation (MGI Ref ID J:86906)
  • arrested at pro-B cell stage
• decreased B cell number (MGI Ref ID J:86906)
  • decrease in peripheral B cells
  • 88% reduction of splenic B cells relative to controls
  • near absence of lymph node B cells
  • detected peripheral B cells did not undergo cre-mediated recombination
• absent pre-B cells (MGI Ref ID J:86906)
• increased B cell apoptosis (MGI Ref ID J:86906)
  • increased apoptosis at pro-B cell stage

Mcl1^tm2Sjk/Mcl1^tm3Sjk Tg(Mx1-cre)1Cgn/0

        involves: 129X1/SvJ   (conditional)

• hematopoietic system phenotype
• decreased B cell number (MGI Ref ID J:86906)
  • peripheral B cells are not maintained
• decreased T cell number (MGI Ref ID J:86906)
  • peripheral T cells are not maintained
• immune system phenotype
• decreased B cell number (MGI Ref ID J:86906)
  • peripheral B cells are not maintained
• decreased T cell number (MGI Ref ID J:86906)
  • peripheral T cells are not maintained

View Research Applications

Research Applications

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

Apoptosis Research
Endogenous Regulators

Immunology and Inflammation Research
Autoimmunity (B and T cell deficiency)
Immunodeficiency (B and T cell deficiency)
Inflammation (B and T cell deficiency)
Lymphoid Tissue Defects (B and T cell deficiency)
Lymphoid Tissue Defects (hematopoietic development)

Reproductive Biology Research
Fertility Defects

Research Tools
Apoptosis Research
Cre-lox System (loxP-flanked Sequences)
Immunology and Inflammation Research (B and T cell deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Mcl1tm3Sjk
Allele Name		targeted mutation 3, Stanley J Korsmeyer
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		F-Mcl-1; Mcl-1f; Mcl-1flox;
Mutation Made By		Stanley Korsmeyer,   Dana-Farber Cancer Institute
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Mcl1, myeloid cell leukemia sequence 1
Chromosome		3
Gene Common Name(s)		AW556805; BCL2L3; EAT; MCL1L; MCL1S; MGC104264; MGC1839; Mcl-1; TM; expressed sequence AW556805;
Molecular Note		Single loxP sites flanked exon 1 which contains the start codon. Western blot analysis of lysates of thymocytes showed the level of protein in mutant mice to be comparable to that in wild-type mice. [MGI Ref ID J:86906]

Genotyping

Genotyping Information

Genotyping Protocols

Mcl1^tm3Sjk, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Mcl1^tm3Sjk related

Arbour N; Vanderluit JL; Le Grand JN; Jahani-Asl A; Ruzhynsky VA; Cheung EC; Kelly MA; MacKenzie AE; Park DS; Opferman JT; Slack RS. 2008. Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. J Neurosci 28(24):6068-78. [PubMed: 18550749]  [MGI Ref ID J:137346]

Opferman JT; Iwasaki H; Ong CC; Suh H; Mizuno S; Akashi K; Korsmeyer SJ. 2005. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 307(5712):1101-4. [PubMed: 15718471]  [MGI Ref ID J:96127]

Opferman JT; Letai A; Beard C; Sorcinelli MD; Ong CC; Korsmeyer SJ. 2003. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426(6967):671-6. [PubMed: 14668867]  [MGI Ref ID J:86906]

Woodland RT; Fox CJ; Schmidt MR; Hammerman PS; Opferman JT; Korsmeyer SJ; Hilbert DM; Thompson CB. 2008. Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood 111(2):750-60. [PubMed: 17942753]  [MGI Ref ID J:130058]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes. Homozygous males have severely reduced fertility. As these mice are on a mixed B6;129X1 background, coat color variations may be observed in litters (including black, pink-eyed light chinchilla or albino).
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

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

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Contact Information
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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

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional 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.