Strain Name:
B6.129S4-Sos1tm1.2Rak/Mmjax
Stock Number:
037588-JAX
Citation ID:
RRID:MMRRC_037588-JAX
Other Names:
Sos1 E846K, EK

Strain Information

Sos1tm1.2Rak
Name: SOS Ras/Rac guanine nucleotide exchange factor 1; targeted mutation 1.2, Raju Kucherlapati
Synonyms: Sos1E846K, Sos1E846K
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 17
Alteration at locus: Knock-In
Sos1
Name: SOS Ras/Rac guanine nucleotide exchange factor 1
Synonyms: 4430401P03Rik
Type: Gene
Species: Mouse
Chromosome: 17
Alteration at locus: Knock-In
NCBI: 20662
VEGA: 17
Homologene: 4117
Genetic Alterations
These Sos1E846K mutant mice exhibit phenotypes consistent with several features of Noonan syndrome including: cardiac hypertrophy, short stature, triangular faces and blunt snouts, splenomegaly, and hematologic disorders. Most homozygous embryos die due to cardiac defects.
ES Cell Line
J1
Phenotype
SOS1 (son of sevenless homolog 1) encodes a RAS and RAC guanine nucleotide exchange factor (GEF) and is involved regulation of the RAS/ERK/MAPK pathway. Mutations in this gene are associated with Noonan syndrome (NS), an autosomal dominant disorder characterized by with congenital heart disease, short stature, facial abnormalities and myeloproliferative disease. 10-15% of NS patients have mutations in Sos1. The E846K allele is a missense mutation that causes a conformational change resulting in constitutive activation of the RAS/MAPK pathway.


Most homozygous embryos die between E10.5 and the neonatal stage from multiple cardiac defects including atrial/ventricular septal defects, aortic valvular stenosis, ventricular hypertrophy and pericardial effusions. Surviving homozygous mice do not live beyond 10 months of age. Heterozygotes exhibit left ventricular cardiac hypertrophy, short stature, shortened skull length with triangular faces and blunt snouts, splenomegaly, and increased numbers of neutrophils and leukocytes.

Mammalian Phenotype Terms
Allelic Composition: Sos1tm1.2Rak/Sos1tm1.2Rak (Genetic Background: involves: 129S/Sv * C57BL/6 * FVB/N * SJL )

Allelic Composition: Sos1tm1.2Rak/Sos1+ (Genetic Background: involves: 129S/Sv * C57BL/6 * FVB/N * SJL )

MeSH Terms
  • Animals
  • Disease Models, Animal
  • Female
  • Heart/embryology
  • Heterozygote
  • Homozygote
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Mutation
  • Noonan Syndrome/embryology
  • Noonan Syndrome/genetics
  • Noonan Syndrome/metabolism
  • Phenotype
  • Pregnancy
  • SOS1 Protein/genetics
  • STAT3 Transcription Factor/metabolism
  • Signal Transduction
  • rac GTP-Binding Proteins/metabolism
Strain Development
The targeting vector is designed as a unidirectional Cre-mediated recombination system. The vector contains a wild-type loxP (wloxP) site upstream of exon 16, a mutant loxP (mloxP) site downstream of exon 16, an inverted exon 16 with the amino acid substitution E846K, followed by wloxP and mloxP sites and an FRT-flanked neomycin cassette. The mloxP sites preferentially recombine with each other, as do the wloxP sites. The E846K mutation results in a glutamic acid to lysine change at position 846. The construct was electroporated into 129S4/SvJae –derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to B6.Cg-Tg(ACTFLPe)9205Dym/J to remove the neomycin cassette, followed by a cross to unspecified EIIA-cre mice on a C57BL/6 background . Following Cre exposure, the inverted exon 16 (with the E846K mutation) moved into the correct orientation and the endogenous exon 16 was removed. Heterozygous mice were mated and offspring lacking the Cre transgene were crossed to C57BL/6 mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
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 csmmrrc@jax.org. Older strains may not have this information.
  • Cancer
  • Cardiovascular
  • Developmental Biology
  • Hematology
  • Model for Human Disease
    • Noonan Syndrome
Donor
Raju Kucherlapati, Ph.D., Harvard Medical School.
Benjamin G. Neel, M.D., Ontario Cancer Institute.
Primary Reference

Chen PC, Wakimoto H, Conner D, Araki T, Yuan T, Roberts A, Seidman C, Bronson R, Neel B, Seidman JG, Kucherlapati R. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome-associated Sos1 mutation. J Clin Invest. 2010 Dec;120(12):4353-65. (Medline PMID: 21041952)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-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 csmmrrc@jax.org.
Coat Color
Black
MMRRC Breeding System
Backcross
Generation
Over 10
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: N/A N/A
Heterozygotes are fertile: N/A N/A
Age Reproductive Decline: > 12 months > 12 months
Average litter size
5-9
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 csmmrrc@jax.org 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
037588-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
037588-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

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.