Allele Symbol: Slfn2m1Btlr Name: mutation 1, Bruce Beutler Alteration at locus: Chemically Induced
Genetic Alterations:
An ENU-induced T to A
transversion occurred at position 586 of the Slfn2 gene (Genbank Accession NM_011408).
The recessive mutation results in an isoleucine to asparagine change at position
135 of the Schlafen2 protein.
Phenotype Homozygous phenotype: Homozygous
mice show increased susceptibility to infection by mouse cytomegalovirus (MCMV),
listeria monocytogenes, and lymphocytic choriomeningitis virus (LCMV). Natural
killer (NK) cell numbers are significantly increased in the thymus, spleen
and liver of homozygotes, while low T cell (both CD4 and CD8) numbers are seen
in the spleen and lymph node, and low CD8 and slightly reduced CD4 T cell numbers
are seen in the blood. When transferred to an irradiated congenic host, homozygous
elektra T cells fail to repopulate the spleen, however, elektra B cells reconstitute
the spleen normally. Bcl-2 expression is specifically reduced in homozygous
elektra CD8+CD44(high) T cells, but is normal in CD8+CD44(low) T cells.
Heterozygous phenotype: Wild-type.
Mammalian Phenotype Terms:(provided by MGI)Extend all MPTs assigned by genotype
Slfn2m1Btlr/Slfn2m1Btlr
C57BL/6J-Slfn2<m1Btlr>
mortality/aging
increased susceptibility to bacterial infection induced morbidity/mortality (MGI Ref ID J:158985)
4 to 5 days after intravenous injection with Listeria monocytogenes, mice die unlike similarly treated wild-type mice
increased susceptibility to viral infection induced morbidity/mortality (MGI Ref ID J:158985)
6 to 8 days following inoculation with MCMV (mouse cytomegalovirus), all mice die unlike similarly treated wild-type mice
however, transplantation of wild-type bone marrow rescues induced lethality
immune system phenotype
abnormal leukocyte physiology (MGI Ref ID J:158985)
based on marker expression, T cells exhibit in a semi-activated state unlike in wild-type mice
T cells from bone marrow transplants into Cd3em1Btlr mice exhibit a semi-activated state unlike similarly treated T cells derived from transplanted wild-type bone marrow
abnormal T cell proliferation (MGI Ref ID J:158985)
after 24 hours, TCR stimulation produces a greater proportion of activation-competent cells compared with similarly treated cells
decreased T cell proliferation (MGI Ref ID J:158985)
CD4+ T cells and CD8+ T cells fail to proliferate in response to anti-CD3 and anti-CD28 antibodies or PMA and ionomycin unlike similarly treated wild-type mice
after 48 hours, TCR stimulation produces a fewer replicative CD8+ T cells compared with similarly treated cells
48 hours after TCR stimulation, T cell apoptosis is higher than in similarly treated wild-type cells
however, gamma radiation-induced apoptosis is normal and Tg(BCL2)25Wehi rescues increased apoptosis
decreased CD4-positive T cell number (MGI Ref ID J:158985)
the percent of CD4+ cells in the spleen and lymph is reduced compared to in wild-type mice
decreased CD8-positive T cell number (MGI Ref ID J:158985)
the percent of CD8+ cells in the spleen, lymph, and blood is reduced compared to in wild-type mice
LCMV-infected mice have fewer CD8+ T cells than in similarly treated wild-type mice
restimulation of splenocytes from LCMV-infected mice results in fewer IFN-gamma-producing CD8+ T cells compared with similarly treated wild-type mice
decreased monocyte cell number (MGI Ref ID J:158985)
mice exhibit a slightly lower percent of monocytes in the blood and spleen compared with wild-type mice
L. monocytogenes-infected mice exhibit lower monocytes in the blood and spleen compared with similarly treated wild-type mice
increased neutrophil cell number (MGI Ref ID J:158985)
L. monocytogenes-infected mice exhibit increased neutrophil percent compared with similarly treated wild-type mice
increased susceptibility to bacterial infection (MGI Ref ID J:158985)
L. monocytogenes-infected mice exhibit lower monocytes in the blood and spleen compared with similarly treated wild-type mice
increased susceptibility to bacterial infection induced morbidity/mortality (MGI Ref ID J:158985)
4 to 5 days after intravenous injection with Listeria monocytogenes, mice die unlike similarly treated wild-type mice
increased susceptibility to viral infection (MGI Ref ID J:158985)
mice exhibit impaired clearance of LCMV (lymph ocytic choriomeningitis virus) compared with similarly treated wild-type mice
LCMV-infected mice have fewer CD8+ T cells than in similarly treated wild-type mice
restimulation of splenocytes from LCMV-infected mice results in fewer IFN-gamma-producing CD8+ T cells compared with similarly treated wild-type mice
increased susceptibility to viral infection induced morbidity/mortality (MGI Ref ID J:158985)
6 to 8 days following inoculation with MCMV (mouse cytomegalovirus), all mice die unlike similarly treated wild-type mice
however, transplantation of wild-type bone marrow rescues induced lethality
homeostasis/metabolism phenotype
abnormal nitric oxide homeostasis (MGI Ref ID J:158985)
monocytes treated with IFN-gamma and heat-killed L. monocytogenes fail to exhibit as great an increase in nitric oxide as in similarly treated wild-type cells
based on marker expression, T cells exhibit in a semi-activated state unlike in wild-type mice
T cells from bone marrow transplants into Cd3em1Btlr mice exhibit a semi-activated state unlike similarly treated T cells derived from transplanted wild-type bone marrow
abnormal T cell proliferation (MGI Ref ID J:158985)
after 24 hours, TCR stimulation produces a greater proportion of activation-competent cells compared with similarly treated cells
decreased T cell proliferation (MGI Ref ID J:158985)
CD4+ T cells and CD8+ T cells fail to proliferate in response to anti-CD3 and anti-CD28 antibodies or PMA and ionomycin unlike similarly treated wild-type mice
after 48 hours, TCR stimulation produces a fewer replicative CD8+ T cells compared with similarly treated cells
decreased CD4-positive T cell number (MGI Ref ID J:158985)
the percent of CD4+ cells in the spleen and lymph is reduced compared to in wild-type mice
decreased CD8-positive T cell number (MGI Ref ID J:158985)
the percent of CD8+ cells in the spleen, lymph, and blood is reduced compared to in wild-type mice
LCMV-infected mice have fewer CD8+ T cells than in similarly treated wild-type mice
restimulation of splenocytes from LCMV-infected mice results in fewer IFN-gamma-producing CD8+ T cells compared with similarly treated wild-type mice
decreased monocyte cell number (MGI Ref ID J:158985)
mice exhibit a slightly lower percent of monocytes in the blood and spleen compared with wild-type mice
L. monocytogenes-infected mice exhibit lower monocytes in the blood and spleen compared with similarly treated wild-type mice
increased neutrophil cell number (MGI Ref ID J:158985)
L. monocytogenes-infected mice exhibit increased neutrophil percent compared with similarly treated wild-type mice
Founder genetic background: C57BL/6J
Strain genetic background: C57BL/6J
Strain Development: The original mutant
was a C57BL/6J G3 ENU-induced mutant; all subsequent crosses to maintain the
strain were on a C57BL/6J background only.
Suggested Control Mice:
Wild-type littermates
C57BL/6J
Research Applications
Apoptosis
Immunology and inflammation
Research tools
Strain Origin
Donor:
Bruce Beutler, M.D.,
The Scripps Research Institute, La Jolla, CA
Primary Reference:
Berger M, Moresco E, Beutler
B. Record for “elektra”,
updated March 15, 2010. MUTAGENETIX (TM), B. Beutler and colleagues, Department
of Genetics, The Scripps Research Institute, La Jolla, CA.
Berger M; Krebs P; Crozat K; Li X; Croker BA; Siggs OM; Popkin D; Du X; Lawson BR; Theofilopoulos AN; Xia Y; Khovananth K; Y Moresco EM; Satoh T; Takeuchi O; Akira S; Beutler B, An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence., Nat Immunol 2010 Apr;11(4):335-43
(Medline PMID: 20190759)
Berger M; Krebs P; Crozat K; Li X; Croker BA; Siggs OM; Popkin D; Du X; Lawson BR; Theofilopoulos AN; Xia Y; Khovananth K; Y Moresco EM; Satoh T; Takeuchi O; Akira S; Beutler B, An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence., Nat Immunol 2010 Apr;11(4):335-43
(Medline PMID: 20190759)
Colony and Husbandry Information
Appearance
Coat color: Black
Other:
Breeding
MMRRC Breeding System: Random intra-strain mating
Breeding Scheme(s):
Homozygous female
x Homozygous male
Heterozygous female x
Heterozygous male
Generation:
Overall Breeding Performance: Good
Reproductive Statistics
Viability and Fertility:
Female
Male
Homozygotes are viable:
Yes
Yes
Homozygotes are fertile:
Yes
Yes
Heterozygotes are fertile:
Yes
Yes
Age Reproductive Decline:
Unknown
Unknown
Average litter size: 4-6
Recommended wean age: 3 weeks
Special Considerations
None
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@ucdavis.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
031705-UCD-RESUS
Litter recovered from cryo-archive
$2,022.00
Non-Profit
Litter
Recovered litter1; additional fees for any special requests.
031705-UCD-SPERM
Cryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot
Approximate quantity.2
031705-UCD-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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