Allele Symbol: Thy1a Name: a variant Chromosome: 9 Alteration at locus: Spontaneous Mutation
Allele Symbol: Foxp3sf Name: scurfy Alteration at locus: Spontaneous Mutation
Genetic Alterations:
Scurfy is a spontaneous mutation in the foxp3 gene on the X-chromosome.
Genotype Determination:
The genotyping protocol for this strain is currently not available. The MMRRC will develop a protocol if this strain is ordered.
ES Cell Line: Not applicable
Strain Description
Phenotype Homozygous phenotype: Not applicable
Hemizygous phenotype: Hemizygous males die at 25-35 days of age with immune dysregulation and cytokine toxicity.
Scurfy males lack CD4+CD25+ regulatory T cells. Clinical signs include enlarged lymph nodes,
hepatosplenomegaly, scaly skin, anemia, diarrhea.
Mammalian Phenotype Terms:(provided by MGI)Extend all MPTs assigned by genotype
The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
tissue has dense predominantly peribronchovascular infiltrates, composed of CD4+ and Cd8+ T cells
Foxp3sf/-
B6.Cg-Foxp3<sf>
hematopoietic system phenotype
abnormal CD4-positive T cell morphology (MGI Ref ID J:82560)
decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number (MGI Ref ID J:82560)
at 10 days of age there are significantly fewer CD4+ CD25+ T cells in the lymph nodes and thymus compared with controls and transfer of CD4+ CD25+ T cells from wild-type donors into 1- to 2-day old hemizygous pups rescues the disease phenotype
abnormal megakaryocyte progenitor cell morphology (MGI Ref ID J:167802)
mutants exhibit about a 50% reduction in megakaryocyte progenitors
decreased megakaryocyte cell number (MGI Ref ID J:167802)
mutants exhibit about 4-fold less mature bone marrow megakaryocytes than controls
decreased platelet cell number (MGI Ref ID J:167802)
mutants exhibit up to 53% fewer platelets than controls
increased mean platelet volume (MGI Ref ID J:167802)
mutants exhibit reduced serum levels of TGF-beta and increased serum levels of CD40L, TXB2, and 12(S)-HETE, suggesting altered platelet release
immune system phenotype
abnormal CD4-positive T cell morphology (MGI Ref ID J:82560)
decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number (MGI Ref ID J:82560)
at 10 days of age there are significantly fewer CD4+ CD25+ T cells in the lymph nodes and thymus compared with controls and transfer of CD4+ CD25+ T cells from wild-type donors into 1- to 2-day old hemizygous pups rescues the disease phenotype
abnormal CD4-positive T cell physiology (MGI Ref ID J:82560)
CD4+ CD25+ T cells from 28 day old lymph nodes proliferate abnormally in response to TCR stimulation and fail to provide suppressor activity
transfer of CD4+ T cells from hemizygotes into RAG1 deficient hosts transfers the wasting disease and colitis and co-transfer of CD4+ CD25+ from wild-type donors prevents the development of this disease
Foxp3sf/-
either: 129Rl.Cg-Foxp3<sf> or (involves: 101/Rl * C3Hf/Rl * STOCK MR)
abnormal lymph node morphology (MGI Ref ID J:11262)
lesions in the lymph nodes that contain a randomly distributed mixture of lymphoblasts, blastlike mononuclear cells with vesicular nuclei, hypertrophic ret iculum cells, macrophages, and granulocytes instead of small lymphocytes
complete loss of normal architecture
abnormal lymph node B cell domain morphology (MGI Ref ID J:11262)
lack of discernible follicles
abnormal lymph node T cell domain morphology (MGI Ref ID J:11262)
no distinct paracortex
abnormal lymph node medullary cord morphology (MGI Ref ID J:11262)
subcutaneous lymph nodes such as inguinal, axillary, and cervical nodes and consistently enlarged while visceral lymph nodes are slightly or moderately enlarged
abnormal lymphocyte morphology (MGI Ref ID J:11262)
exhibit lymphoproliferative lesions
abnormal macrophage morphology (MGI Ref ID J:11262)
mild to moderate sinus histiocytosis in the lymph nodes
abnormal spleen white pulp morphology (MGI Ref ID J:11262)
white pulp may be enlarged or shrunken and is composed of blastlike mononuclear cells with vesicular nuclei, prominent reticulum cells, lymphoblasts, and variable number of plasma cells
occasional erythrophagocytic macrophages and plasma cells with Russel's bodies can be seen at the margins of the white pulp
abnormal spleen B cell follicle morphology (MGI Ref ID J:11262)
follicles are lacking and lymphocytes are absent in the spleen
abnormal spleen white pulp morphology (MGI Ref ID J:11262)
white pulp may be enlarged or shrunken and is composed of blastlike mononuclear cells with vesicular nuclei, prominent reticulum cells, lymphoblasts, and variable number of plasma cells
occasional erythrophagocytic macrophages and plasma cells with Russel's bodies can be seen at the margins of the white pulp
abnormal spleen B cell follicle morphology (MGI Ref ID J:11262)
follicles are lacking and lymphocytes are absent in the spleen
Strain Development: 129/Rl-sf N105 obtained from ORNL in 2000. BALB/c-Thy1.1 obtained from Shimon Sakaguchi
(Japan) and congenic strain was created by 10 backcrosses to this BALB/c substrain.
Suggested Control Mice:
Wildtype littermates
Research Applications
Immunology and Inflammation
Models for Human Disease
Strain Origin
Donor:
Virginia Godfrey, DVM, Ph.D., University of North Carolina
Primary Reference:
Ramsdell F. Foxp3 and natural regulatory T cells: key to a cell lineage?
Immunity. 2003 Aug;19(2):165-8. Review.
(Medline PMID: 12932350)
Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
Nat Immunol. 2003 Apr;4(4):330-6. Epub 2003 Mar 3.
(Medline PMID: 12612578)
Special Considerations
Scurfy males are very susceptible to colitis induced by Helicobacter infection. This strain
is best maintained in sterilized microisolator conditions that prevent the introduction of
Helicobacter sp.
Health Status Report
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.
Order Request Information
Availability Level:
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Conditions of Distribution:
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.
Fees:
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
010500-UNC-RESUS
Litter recovered from cryo-archive
$2,022.00
Non-Profit
Litter
Recovered litter1; additional fees for any special requests.
010500-UNC-EMBRYO
Cryo-preserved embryos
$1,038.00
Non-Profit
Aliquot
Approximate quantity3: 20-40 embryos / aliquot
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 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.
The MMRRC is a collaborative effort, funded by grants from the
NIH
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