Description

Strain Information

Former Names 129S(FVB)-Men1tm1Ctre/J    (Changed: 26-JAN-07 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Francis Collins,   NHGRI/NIH

Description
These mice possess loxP sites flanking exons 3 to 8 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

When bred to a strain expressing Cre recombinase in pancreatic beta cells (see Stock No. 003573 for example), this mutant mouse strain may be useful in studies of pancreatic islet adenomas.

Development
A loxP site flanked targeting vector containing a loxP-bracketed neomycin resistance gene under the control of the mouse phosphoglycerate kinase promoter was inserted into intron 2 of the Men1 gene. Another loxP site was positioned within intron 8. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were bred to 129S6/SvEvTacFBR females. The progeny were heterozygous for the floxed allele (TSM/+). These heterozygous mice were bred with a ubiquitously expressing cre mouse line (Ella-cre) on an an FVB background. The resulting mice were heterozygous for an allele that lacked the PGK-neo cassette but contained loxP sites in introns 2 and 8, flanking exons 3 to 8.

Related Strains

Strains carrying other alleles of Men1

004066

FVB;129S-Men1tm1.1Ctre/J

View Strains carrying other alleles of Men1     (1 strain)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Men1^tm1Ctre/Men1⁺ Tg(Ins2-cre)25Mgn/0

        involves: 129S6/SvEvTac * C57BL/6 * FVB/N   (conditional)

• tumorigenesis
• insulinoma (MGI Ref ID J:85042)
  • heterozygous mutants develop islet tumors later than homozygous mutants

Men1^tm1Ctre/Men1^tm1Ctre Tg(Ins2-cre)25Mgn/0

        involves: 129S6/SvEvTac * C57BL/6 * FVB/N   (conditional)

• endocrine/exocrine gland phenotype
• islet cell hyperplasia (MGI Ref ID J:85042)
  • abnormally large islets with pleomorphic cells of variable size and shape are seen at 4 weeks of age
  • in 60 week old mutants islet volume has increased 20- to 26-fold
• homeostasis/metabolism phenotype
• decreased circulating glucose level (MGI Ref ID J:85042)
  • fasting blood glucose levels are decreased
• increased circulating insulin level (MGI Ref ID J:85042)
  • fasting serum insulin levels are increased
• tumorigenesis
• insulinoma (MGI Ref ID J:85042)
  • foci of adenoma develop within the hyperplastic islets by 20 - 28 weeks of age and multiple adenomas are seen by 23 weeks of age
  • 19 of 34 homozygous floxed mutants had adenomas by the date of the scheduled autopsy and tumor incidence in homozygous mutants correlates to the level of Cre expression for the different cre transgenes
  • a sex bias is seen with 13 of 16 virgin females developing adenomas compared to 6 of 18 males
• digestive/alimentary phenotype
• islet cell hyperplasia (MGI Ref ID J:85042)
  • abnormally large islets with pleomorphic cells of variable size and shape are seen at 4 weeks of age
  • in 60 week old mutants islet volume has increased 20- to 26-fold

View Research Applications

Research Applications

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

Research Tools
Cre-lox System (loxP-flanked Sequences)

Men1^tm1Ctre related

Cancer Research
Increased Tumor Incidence (Adenomas: pancreatic b cells)
Increased Tumor Incidence (Other Tissues/Organs, multiple endocrine tissues)
Tumor Suppressor Genes

Diabetes and Obesity Research
Pancreatic B Cell Adenomas

Mouse/Human Gene Homologs
multiple endocrine neoplasia, type I

Research Tools
Developmental Biology Research (Cre-lox System)
Endocrine Deficiency Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Men1tm1Ctre
Allele Name		targeted mutation 1, Judy S Crabtree
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Men1TSM; Men1loxP;
Mutation Made By		Judy Crabtree,   Wyeth Pharmaceuticals
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Men1, multiple endocrine neoplasia 1
Chromosome		19
Gene Common Name(s)		AW045611; MEAI; MGC114329; SCG2; expressed sequence AW045611; menin;
Molecular Note		A loxP-flanked neomycin selection cassette was inserted into intron 2 and a third loxP site was inserted into intron 8. [MGI Ref ID J:67128]

Genotyping

Genotyping Information

Genotyping Protocols

Men1^tm1Ctre, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Crabtree JS; Scacheri PC; Ward JM; McNally SR; Swain GP; Montagna C; Hager JH; Hanahan D; Edlund H; Magnuson MA; Garrett-Beal L; Burns AL; Ried T; Chandrasekharappa SC; Marx SJ; Spiegel AM; Collins FS. 2003. Of mice and MEN1: Insulinomas in a conditional mouse knockout. Mol Cell Biol 23(17):6075-85. [PubMed: 12917331]  [MGI Ref ID J:85042]

Additional References

Crabtree JS; Scacheri PC; Ward JM; Garrett-Beal L; Emmert-Buck MR; Edgemon KA; Lorang D; Libutti SK; Chandrasekharappa SC; Marx SJ; Spiegel AM; Collins FS. 2001. A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc Natl Acad Sci U S A 98(3):1118-23. [PubMed: 11158604]  [MGI Ref ID J:67128]

Men1^tm1Ctre related

Chen YX; Yan J; Keeshan K; Tubbs AT; Wang H; Silva A; Brown EJ; Hess JL; Pear WS; Hua X. 2006. The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression. Proc Natl Acad Sci U S A 103(4):1018-23. [PubMed: 16415155]  [MGI Ref ID J:105708]

Crabtree JS; Scacheri PC; Ward JM; Garrett-Beal L; Emmert-Buck MR; Edgemon KA; Lorang D; Libutti SK; Chandrasekharappa SC; Marx SJ; Spiegel AM; Collins FS. 2001. A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc Natl Acad Sci U S A 98(3):1118-23. [PubMed: 11158604]  [MGI Ref ID J:67128]

La P; Yang Y; Karnik SK; Silva AC; Schnepp RW; Kim SK; Hua X. 2007. Menin-mediated caspase 8 expression in suppressing multiple endocrine neoplasia type 1. J Biol Chem 282(43):31332-40. [PubMed: 17766243]  [MGI Ref ID J:126366]

Scacheri PC; Crabtree JS; Kennedy AL; Swain GP; Ward JM; Marx SJ; Spiegel AM; Collins FS. 2004. Homozygous loss of menin is well tolerated in liver, a tissue not affected in MEN1. Mamm Genome 15(11):872-7. [PubMed: 15672591]  [MGI Ref ID J:96272]

Schnepp RW; Chen YX; Wang H; Cash T; Silva A; Diehl JA; Brown E; Hua X. 2006. Mutation of tumor suppressor gene Men1 acutely enhances proliferation of pancreatic islet cells. Cancer Res 66(11):5707-15. [PubMed: 16740708]  [MGI Ref ID J:110111]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

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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Contact Information
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Fax: 207.288.6150
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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.

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.”

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