Strain Name:
FVB;129S1-Rettm3Cos/Mmucd
Stock Number:
036721-UCD
Citation ID:
RRID:MMRRC_036721-UCD
Other Names:
Ret-S697A, Rettm2Mat

Strain Information

Rettm3Cos
Name: ret proto-oncogene; targeted mutation 3, Frank Costantini
Synonyms: Rettm2Mat, c-Ret-KIS697A
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 6
Alteration at locus: Knock-In
Ret
Name: ret proto-oncogene
Synonyms: c-Ret, RET51, RET9
Type: Gene
Species: Mouse
Chromosome: 6
Alteration at locus: Knock-In
NCBI: 19713
HGNC: HGNC:9967
Homologene: 7517
Genetic Alterations
A targeting vector was designed to insert the S697A mutation into exon 11. A neo cassette included in the vector was removed by crossing with mice expressing cre recombinase in the germline.
Genotype Determination
ES Cell Line
W9.5/W95 derived from 129S1/Sv-Oca2+ Tyr+ Kitl+
Phenotype

Homozygous: Homozygotes lack the enteric nervous system in the distal colon, resulting from a migration defect of enteric neural crest cells (ENCCs). This causes megacolon, similar to Hirschsprung disease in humans. These mutant mice may provide useful models to study the molecular mechanisms of development of Hirschsprung's disease.

Heterozygous: Same as wild-type.

Mammalian Phenotype Terms
Allelic Composition: Rettm3Cos/Rettm3Cos (Genetic Background: involves: 129S1/Sv * FVB/N )

MeSH Terms
  • Animals
  • Anthracenes/pharmacology
  • Carbazoles/pharmacology
  • Cell Movement/drug effects
  • Cell Movement/physiology
  • Colon/innervation
  • Enteric Nervous System/embryology
  • Glial Cell Line-Derived Neurotrophic Factor/metabolism
  • Indoles/pharmacology
  • Mice
  • Mice, Mutant Strains
  • Mutation/genetics
  • Neural Crest/physiology
  • Proto-Oncogene Proteins c-ret/genetics
  • Pyrroles/pharmacology
  • Signal Transduction/physiology
  • Amino Acid Substitution/genetics
  • Deafness/complications
  • Deafness/enzymology
  • Enzyme Activation
  • Gene Knock-In Techniques
  • Hearing Loss/complications
  • Hearing Loss/congenital
  • Hearing Loss/enzymology
  • Hirschsprung Disease/complications
  • Hirschsprung Disease/enzymology
  • Immunohistochemistry
  • NF-kappa B/metabolism
  • Nerve Degeneration/enzymology
  • Nerve Degeneration/pathology
  • Neurons/enzymology
  • Neurons/pathology
  • Neurons/ultrastructure
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt/metabolism
  • Proto-Oncogene Proteins c-ret/metabolism
  • Spiral Ganglion/enzymology
  • Spiral Ganglion/pathology
  • Spiral Ganglion/ultrastructure
Strain Development
The mutation S697A was introduced into the mouse Ret gene by targeted mutagenesis in W9.5 ES cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts, and the RET S697A mutation transmitted through the germline (RETS697A-neo). To remove the neo gene, RETS697A-neo mice were crossed with β-actin promoter/Cre transgenic mice, FVB/N-TgN(ACTB-Cre)2Mrt, and excision of the neo gene was confirmed by Southern blotting. The mice were subsequently backcrossed to strain 129S1.
Suggested Control Mice
Wild-type littermates
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.
  • Developmental Biology
  • Internal Organ
  • Neurobiology
  • Model of Human Disease
    • Hirschsprung disease
Donor
Frank Costantini, Ph.D., Columbia University Medical Center.
Primary Reference

Asai N, Fukuda T, Wu Z, Enomoto A, Pachnis V, Takahashi M, Costantini F. Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells. Development. 2006 Nov;133(22):4507-16. (Medline PMID: 17050626).

Ohgami N, Ida-Eto M, Shimotake T, Sakashita N, Sone M, Nakashima T, Tabuchi K, Hoshino T, Shimada A, Tsuzuki T, Yamamoto M, Sobue G, Jijiwa M, Asai N, Hara A, Takahashi M, Kato M. c-Ret-mediated hearing loss in mice with Hirschsprung disease. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13051-6. (Medline PMID: 20616061).

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.
MMRRC Breeding System
Backcross
Breeding Scheme(s)

Wild-type (129S1) female x Heterozygous male or reciprocal mating

Generation
N3
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Reduced Reduced
Homozygotes are fertile: Unknown Unknown
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
Undetermined
Recommended wean age
3-4 weeks

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
036721-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
036721-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
036721-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.