Strain Name    : B6;129S-S1pr1tm1Rlp/Mmnc

Stock Number : 000035-UNC

Gene Information

(provided by MGI)
Allele Symbol: S1pr1tm1Rlp
Name: targeted mutation 1, Richard L Proia
Chromosome: 3
Alteration at locus: Knockout
Gene Symbol: S1pr1
Name: sphingosine-1-phosphate receptor 1
Chromosome: 3
Alteration at locus: Knockout
Genetic Alterations:
LacZ-neo was inserted into exon 2 of the target gene.

Genotype Determination:

ES Cell Line: TC1/TC-1

Phenotype

Embryonic lethal at E12.5-13.5; massive bleeding; defect in vascular maturation.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
S1pr1tm1Rlp/S1pr1tm1Rlp
        involves: 129S6/SvEvTac * C57BL/6
  • mortality/aging
    • complete lethality throughout fetal growth and development (MGI Ref ID J:71961)
      • die between E12.5 and E14.5; no surviving mutants past E14.5
    • complete lethality throughout fetal growth and development (MGI Ref ID J:106055)
  • embryogenesis phenotype
    • abnormal visceral yolk sac morphology (MGI Ref ID J:71961)
      • yolk sacs display progressive edema and normal vasculature but with less blood
  • cardiovascular system phenotype
    • abnormal blood vessel morphology (MGI Ref ID J:71961)
      • exhibit a defect in blood vessel maturation, however vasculogenesis and angiogenesis appear normal
      • small vessels in the forebrain are dilated
      • abnormal pericyte morphology (MGI Ref ID J:71961)
        • reduction of pericytes in vessels and absence of capillary pericytes
      • abnormal vascular endothelial cell morphology (MGI Ref ID J:71961)
        • endothelial cell body is very thin and in some areas, fragmented, resulting in a discontinuous endothelial cell layer
        • endothelial cell nuclei of capillaries are abnormally rounded and enlarged
      • abnormal vascular smooth muscle morphology (MGI Ref ID J:71961)
        • exhibit vascular smooth muscle defects, with aortae and intracerebral arteries covered only ventrally by poorly organized vascular smooth muscl e cells which are not present along the dorsal surface, however muscular layers in the gastrointestinal tract and bronchial tree are normal
        • vascular smooth muscle cell hypoplasia (MGI Ref ID J:71961)
    • enlarged pericardium (MGI Ref ID J:71961)
    • hemorrhage (MGI Ref IDs J:71961, J:106055)
      • intraembryonic bleeding is evident at E12.5 and is widespread at E13.5 (MGI Ref ID J:71961)
      • bleeding along the body and head at E12.5 (MGI Ref ID J:106055)
    • pericardial edema (MGI Ref ID J:71961)
      • seen at E12.5 and E13.5
  • muscle phenotype
    • abnormal vascular smooth muscle morphology (MGI Ref ID J:71961)
      • exhibit vascular smooth muscle defects, with aortae and intracerebral arteries covered only ventrally by poorly organized vascular smooth muscle cells which are not present along the dorsal surface, however muscular layers in the gastrointestinal tract and bronchial tree are normal
      • vascular smooth muscle cell hypoplasia (MGI Ref ID J:71961)
  • homeostasis/metabolism phenotype
    • edema (MGI Ref ID J:71961)
      • severe edema throughout the body at E13.5
      • pericardial edema (MGI Ref ID J:71961)
        • seen at E12.5 and E13.5
  • limbs/digits/tail phenotype
    • abnormal limb morphology (MGI Ref ID J:71961)
      • limbs are underdeveloped and rounded with areas of bleeding
    • abnormal limb morphology (MGI Ref ID J:106055)
  • cellular phenotype
    • abnormal cell migration (MGI Ref ID J:71961)
      • fibroblasts do not display a significant migratory response to sphingosine-1-phosphate as in wild-type


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
S1pr1tm1Rlp/S1pr1tm1Rlp
        involves: 129S6/SvEvTac
  • nervous system phenotype
    • abnormal forebrain morphology (MGI Ref ID J:103755)
      • massive cell loss in the forebrain at E12.5
      • abnormal diencephalon morphology (MGI Ref ID J:103755)
        • increase in apoptotic cells in the neuroepithelial layers of the diencephalons at E12.5
      • abnormal telencephalon morphology (MGI Ref ID J:103755)
        • increase in apoptotic cells in the neuroepithelial layers of the telencephalon and a decrease in mitotic cell numbers at E12.5
  • immune system phenotype
    • abnormal NK cell differentiation (MGI Ref ID J:154069)
      • in reconstitution experiments, derived NK cells accumulate in the lymph nodes and bone marrow indicating a reduction in NK cell egression from the lymph nodes and bone marrow compared to when wild-type bone marrow is used
      • egression of NK cells from the bone marrow into the bone marrow sinusoids is impaired compared to in wild-type mice
    • decreased NK cell number (MGI Ref ID J:154069)
      • in the bone marrow sinusoids
  • cardiovascular system phenotype
  • hematopoietic system phenotype
    • abnormal NK cell differentiation (MGI Ref ID J:154069)
      • in reconstitution experiments, derived NK cells accumulate in the lymph nodes and bone marrow indicating a reduction in NK cell egression from the lymph nodes and bone marrow compared to when wild-type bone marrow is used
      • egression of NK cells from the bone marrow into the bone marrow sinusoids is impaired compared to in wild-type mice
    • decreased NK cell number (MGI Ref ID J:154069)
      • in the bone marrow sinusoids




Strain of Origin: B6;129S6

Strain genetic background: B6;129S6

Strain Development: 129S6-derived TC-1 ES cells were injected into C57BL/6 blastocysts. Resulting chimeric mice were backcrossed to C57BL/6. Heterozygous siblings then were mated.

Suggested Control Mice:

  • Wildtype littermates

  • Blood vessel development

Donor: Dr. Richard Proia, National Institute of Diabetes and Digestive and Kidney Diseases, NIH

Primary Reference:

Liu, Y., Wada, R. Yamashita, T., Mi, Y., Deng, C.X., Hobson, J.P., Rosenfeldt, H.M., Nava, V.E., Chae, S.S., Lee, M.J., Liu, C.H., Hla, T., Spiegel, S., and Proia, R.L. (2000) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest. 106(8):951-961. (Medline: 11032855)

Colony and Husbandry Information

Maintained in Techniplast ventilated caging, autoclaved cages and water, irradiated feed (PicoLab). Cages are changed in hepa filtered hood. Technicians wear Tyvek suits, head covers, masks, shoe covers, gloves. Gloved hands are dipped in disinfectant when handling cages, mice. Access to breeding area limited to MMRRC personnel.

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_health@med.unc.edu.

Coat color: Black, brown

Other:

MMRRC Breeding System: Intra-strain mate heterozygotes or back-cross to C57BL/6

Breeding Scheme(s):

  • Heterozygous Female x Heterozygous Male
  • Heterozygote x C57BL/6

Generation: Unknown

Overall Breeding Performance:

Breeding Comments: Intra-strain mate heterozygotes, heterozygote x wild type, or backcross to C57BL/6J

Viability and Fertility:FemaleMaleComments
Homozygotes are viable: No No Homozygotes die in utero from d.9.5-13.5 due to hemorrhage. Disruption of gene causes impairment of recruitment of smooth muscle cell to vessel walls.
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Unknown Unknown

Average litter size: 5-6

Recommended wean age: 3 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.

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 $)
Units Notes
000035-UNC-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.

1 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.

2 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.

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

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 above). 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.



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.