Overview

Also Known As:Prf1 KO

Homozygous mutant mice have normal numbers of CD8⁺ T cells and NK cells. CTL and NK cells are unable to lyse virus-infected or allogeneic fibroblasts in vitro. Homozygotes fail to clear lymphocytic choriomeningitis virus. Fibrosarcoma tumor cells are eliminated with reduced efficiency.

Donating Investigator

Dr. Hans Hengartner, University Hospital Zurich

Genetic overview

Genetic Background	Generation
	F?+N3F3pF6 (2021-07-16 00:00:00)

Prf1^tm1Sdz

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Prf1	perforin 1 (pore forming protein)

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Research Applications

Apoptosis Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$218.00 Domestic price for female 4-week

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Details

Detailed Description

Mice homozygous for this perforin-1 targeted mutation are viable and fertile. Homozygous mutant mice have normal numbers of CD8⁺ T cells and NK cells. CTL and NK cells are unable to lyse virus-infected or allogeneic fibroblasts in vitro. Homozygotes fail to clear lymphocytic choriomeningitis virus. Fibrosarcoma tumor cells are eliminated with reduced efficiency.

Development

A replacement vector was used containing the neo gene and which resulted in the disruption of exon 3 of the perforin gene without deletion of coding sequence. No full perforin mRNA was detected by reverse transcription PCR. The targeting construct was introduced into BL/6-III ES cells, which are derived from C57BL/6 male mice.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Kagi D; Ledermann B; Burki K; Seiler P; Odermatt B; Olsen KJ; Podack ER; Zinkernagel RM; Hengartner H. 1994. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice [see comments] Nature 369(6475):31-7PubMed: 8164737 MGI: J:17986

View All References

Genetics

Prf1^tm1Sdz

Allele Symbol: Prf1^tm1Sdz

Allele Name	targeted mutation 1, Sandoz Pharmaceuticals
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	P⁰; perf-; perforin-; perforin 0; Pfn^-; pfp-; Pfp^tm1Sdz; pfpKO; pko; Prf^-; Prf1^-; Prf1^tm/Sdz; prf1^tm1
Gene Symbol and Name	Prf1, perforin 1 (pore forming protein)
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	10
Molecular Note	A neomycin selection cassette was inserted into exon 3. RT-PCR analysis on RNA derived from homozygous mice demonstrated that an abnormal transcript was produced from this allele. However, immunocytochemistry experiments on activated spleen cells derived from homozygous mice confirmed that no detectable protein was made from this allele.
Mutations Made By	Dr. Birgit Lederman, University of Zurich

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

familial hemophagocytic lymphohistiocytosis 2

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

multiple sclerosis

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Prf1^tm1Sdz related

Apoptosis Research
- Extracellular Modulators
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
C.B6-Prf1

endocrine/exocrine gland phenotype

increased T cell derived lymphoma incidence
- in a few mice

respiratory system phenotype

increased lung adenocarcinoma incidence
- in a few mice, with a very late onset
- all are well differentiated papillary adenocarcinomas

neoplasm

abnormal tumor morphology
- some lymphomas have an unusual histiocytic appearance with a pale eosinophilic cytoplasm

increased tumor latency
- in mice on a BALB/c background compared to mice on a C57BL/6 background

increased sarcoma incidence
- in a few mice

increased lung adenocarcinoma incidence
- all are well differentiated papillary adenocarcinomas
- in a few mice, with a very late onset

increased lymphoma incidence
- some mice develop disseminated lymphomas

increased T cell derived lymphoma incidence
- in a few mice

Genotype: Prf1^tm1Sdz/Prf1⁺
A.B6-Prf1

hematopoietic system phenotype

impaired natural killer cell mediated cytotoxicity
- A cytotoxicity assay based on flow cytometric analysis of the number of doubly-labeled NK cell-sensitive Yac-1 target cells that had been labeled with CFSE before and with 7-ADD after incubation with fresh spleen cells demonstrated significantly reduced cytolysis by heterozygous mutant vs. wild-type A/J NK cells (n = 3/genotype; P = 0.0046. Student's t test.)
- ytolysis by heterozygous mutant vs. wild-type A/J NK cells (n = 3/genotype; P = 0.0046. Student's t test.)

immune system phenotype

impaired natural killer cell mediated cytotoxicity
- A cytotoxicity assay based on flow cytometric analysis of the number of doubly-labeled NK cell-sensitive Yac-1 target cells that had been labeled with CFSE before and with 7-ADD after incubation with fresh spleen cells demonstrated significantly reduced cytolysis by heterozygous mutant vs. wild-type A/J NK cells (n = 3/genotype; P = 0.0046. Student's t test.)
- ytolysis by heterozygous mutant vs. wild-type A/J NK cells (n = 3/genotype; P = 0.0046. Student's t test.)

neoplasm

increased incidence of induced tumors
- a significantly greater tumor volume was observed in the NKK-treated heterozygous mutant mice than in the NKK-treated wild-type control mice (P = 0.034)
- 17, heterozygous n = 42; P = 0.031. Mann-Whitney U test.)
- heterozygous mutant female A/J mice treated at 6 weeks of age with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) had developed a significantly greater number of lung adenomas/adenocarcinomas 22 weeks later than NKK-treated wild-type A/J mice (wt n= 17, heterozygous n = 42; P = 0.031. Mann-Whitney U test.)

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
A.B6-Prf1

hematopoietic system phenotype

impaired natural killer cell mediated cytotoxicity
- A cytotoxicity assay based on flow cytometric analysis of the number of doubly-labeled NK cell-sensitive Yac-1 target cells that had been labeled with CFSE before and with 7-ADD after incubation with fresh spleen cells demonstrated significantly reduced cytolysis by homozygous mutant vs. wild-type A/J NK cells. (n = 3/genotype; P = 0.0031. Student's t test.)
- ytolysis by homozygous mutant vs. wild-type A/J NK cells. (n = 3/genotype; P = 0.0031. Student's t test.)

immune system phenotype

impaired natural killer cell mediated cytotoxicity
- A cytotoxicity assay based on flow cytometric analysis of the number of doubly-labeled NK cell-sensitive Yac-1 target cells that had been labeled with CFSE before and with 7-ADD after incubation with fresh spleen cells demonstrated significantly reduced cytolysis by homozygous mutant vs. wild-type A/J NK cells. (n = 3/genotype; P = 0.0031. Student's t test.)
- ytolysis by homozygous mutant vs. wild-type A/J NK cells. (n = 3/genotype; P = 0.0031. Student's t test.)

neoplasm

increased incidence of induced tumors
- Normal - 0.16)
- homozygous mutant female A/J mice treated at 6 weeks of age with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) had developed a significantly greater number of lung adenomas/adenocarcinomas 22 weeks later than had NKK-treated wild-type female A/J mice (wt n= 17, homozygous n = 26; P = 0.036. Mann-Whitney U test.)
- Normal - although a significantly greater tumor volume was observed in NKK-treated heterozygous mutant female mice than in wild-type mice (P = 0.034), the volume of tumors in homozygous mutant mice did not differ significantly from that in wild-type controls (P = 0.16)
- ce (wt n= 17, homozygous n = 26; P = 0.036. Mann-Whitney U test.)

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
involves: BALB/c * C57BL/6

hematopoietic system phenotype

impaired natural killer cell mediated cytotoxicity
- activated splenic NK cells are unable to kill 4T1 or Renca tumor target cells

immune system phenotype

impaired natural killer cell mediated cytotoxicity
- activated splenic NK cells are unable to kill 4T1 or Renca tumor target cells

The following phenotype relates to a compound genotype created using this strain

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
C57BL/6-Prf1

mortality/aging

premature death
- Background Sensitivity - in mice on a C57BL/6 background compared to mice on a BALB/c background

increased sensitivity to induced morbidity/mortality
- all mice die between 40 and 60 days after injection of 10^7 MHC class-I deficient B cell lymphoma cells, while all wild-type mice survive

hematopoietic system phenotype

abnormal NK cell physiology
- impaired ability to clear injected MHC class-I deficient B cell lymphoma cells resulting in increased mortality

decreased cytotoxic T cell cytolysis
- CD8+ T cells cannot lyse in vitro virus-infected, peptide-coated or allogeneic target cells of epithelial, neuroectodermal or mesodermal orgin, however activation and expansion of CD8+ T cells occurs normally

impaired natural killer cell mediated cytotoxicity
- NK-cell-mediated lysis is not evident in the spleen cells after viral infection

abnormal leukocyte physiology

neoplasm

decreased tumor latency
- Background Sensitivity - in mice on a C57BL/6 background compared to mice on a BALB/c background

increased lymphoma incidence
- most lymphomas are diffuse large cell lymphomas
- develop aggressive disseminated lymphomas that affect the spleen, liver and lymph nodes from 300 days of age onwards

increased B cell derived lymphoma incidence
- lymphomas are of a B cell origin or plasmocytomas

reproductive system phenotype

abnormal female reproductive system physiology
- alpha-galactosylceramide induced abortion does not occur

immune system phenotype

decreased cytotoxic T cell cytolysis
- CD8+ T cells cannot lyse in vitro virus-infected, peptide-coated or allogeneic target cells of epithelial, neuroectodermal or mesodermal orgin, however activation and expansion of CD8+ T cells occurs normally

increased susceptibility to bacterial infection
- following infection with IOE, IL-10 production is increased relative to infected wild-type mice
- f contiguous hepatocytes with mild to moderate liver injury, and more macrophage-rich inflammatory infiltrates compared to infected wild-type mice
- following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), mice have a higher burden of bacteria in the liver and lungs but not spleens, develop extensive partially confluent foci of apoptosis or necrosis of contiguous hepatocytes with mild to moderate liver injury, and more macrophage-rich inflammatory infiltrates compared to infected wild-type mice

increased susceptibility to viral infection
- unable to eliminate lymphocytic choriomeningitis virus 12 days after intravenous infection as in controls, with infection eventually leading to weight loss and death between days 13 and 16

abnormal leukocyte physiology

impaired natural killer cell mediated cytotoxicity
- NK-cell-mediated lysis is not evident in the spleen cells after viral infection

abnormal inflammatory response
- fail to develop footpad swelling upon lymphocytic choriomeningitis virus injection into the footpad

increased interleukin-10 secretion
- following infection with a monocytotropic Ehrlichia bacteria from Ixodes ovatrus ticks (IOE), IL-10 production is increased relative to infected wild-type mice

increased susceptibility to infection

increased susceptibility to parasitic infection
- decreased clearance and survival after infection with Trypanosoma cruzi

increased susceptibility to Riboviria infection
- unable to eliminate lymphocytic choriomeningitis virus 12 days after intravenous infection as in controls, with infection eventually leading to weight loss and death between days 13 and 16

abnormal NK cell physiology
- impaired ability to clear injected MHC class-I deficient B cell lymphoma cells resulting in increased mortality

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
C57BL/6-Prf1/J

behavior/neurological phenotype

abnormal behavior
- some chronically infected mice demonstrate minor alterations in stride with normal activity levels, despite presence of demyelination

lethargy
- in LMCV-infected mice

hunched posture
- mutants infected with LCMV display hunched posture 10 days after infection unlike wild-type mice
- in LCMV-infected mice

hypoactivity
- mutants infected with lymphocytic choriomeningitic virus (LCMV) display decreased activity 10 days after infection compared with wild-type controls

integument phenotype

ruffled hair
- mutants infected with LCMV display ruffled fur 10 days after infection when compared with wild-type controls

liver/biliary system phenotype

liver inflammation
- by 10-12 days after LCMV infection, livers show prominent periportal infiltrates

mammalian phenotype

behavior/neurological phenotype
- e at 90 days and 64% by 180 days
- mice infected with TMEV and monitored daily do not show clinical signs of TMEV infecion, including unkempt appearance, decreased spontaneous movement and hind-limb paralysis, at 45 days and 90 days, whereas 12% of susceptible SJL mice show clinical disease at 90 days and 64% by 180 days

immune system phenotype
- delayed type hypersensitivity (DTH) reaction elicited in the ear by intradermal injection of inactive virus is comparable to that of controls

mortality/aging

increased susceptibility to viral infection induced morbidity/mortality
- neutralizing multiple cytokines, including TNF-alpha, IL-12, IL-18, M-CSF, and GM-CSF, with neutralizing antibodies has no effect on survival
- mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias
- mice die 2 weeks after LCMV infection
- mutants die within 2 weeks of lymphocytic choriomeningitic virus (LCMV) infection unlike wild-type mice
- mutants depleted of CD8+ cells (by administration of antibodies against CD8+ cells) survive LCMV infection, however those depleted of CD4+ or NK cells do not survive

increased susceptibility to Riboviria infection induced morbidity/mortality
- neutralizing multiple cytokines, including TNF-alpha, IL-12, IL-18, M-CSF, and GM-CSF, with neutralizing antibodies has no effect on survival
- mutants die within 2 weeks of lymphocytic choriomeningitic virus (LCMV) infection unlike wild-type mice
- mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias
- mutants depleted of CD8+ cells (by administration of antibodies against CD8+ cells) survive LCMV infection, however those depleted of CD4+ or NK cells do not survive

nervous system phenotype

demyelination
- lesions are located mainly in the anterior and anterolateral white matter of the spinal cord; demyelination is chronic and progressive (16% of quadrants at 90 days and 20% of quadrants at 180 days)
- demyelinated axons in close proximity to inflammatory cells and macrophages with intracytoplasmic vacuoles containing myelin debris are seen in mutants, but not in control or other null mice
- at 45 days after infection, foci of demyelination are observed in spinal cord (in 11% of 537 quadrants examined)

brain inflammation
- by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6)
- 30 days after LCMV infection, the meninges show prominent mononuclear infiltrates along the dura
- at 180 days, brain pathology is still present
- by 45 days, inflammation with parenchymal disease is seen in hippocampus, striatum, and corpus callosum in some mice
- persistent inflammation is found in the brainstem of mutants

CNS inflammation
- by 21 days, inflammation with macrophage infiltration persists in the gray matter in mutants but not in controls
- by 7 days after TMEV infection, inflammation is present in the meninges and gray matter of spinal cords in controls as well

abnormal brain meninges morphology
- 30 days after LCMV infection, the meninges show prominent mononuclear infiltrates along the dura

hematopoietic system phenotype

decreased neutrophil cell number
- lack of neutrophilia in LCMV-infected mice

decreased cytotoxic T cell cytolysis
- 2Ics cells
- reduced killing of anti-CD3-loaded P815 target cells, more pronounced than in than in Rab27a^ash and Stx11^tm1.2Ics cells

abnormal cytotoxic T cell physiology
- Normal - however, priming is normal
- impaired CD8+ T cell degranulation

abnormal spleen white pulp morphology
- by 10-12 days after LCMV infection, the white pulp appears chaotic with a prominent infiltrate of macrophages and activated lymphocytes when compared to wild-type spleen

decreased bone marrow cell number
- bone marrow shows severe hypoplasia by 10-12 days after LCMV infection when compared to wild-type mice

decreased leukocyte cell number
- in LCMV-infected mice

decreased NK cell degranulation
- in the presence of recombinant IL15 alone or in combination with IL2

abnormal lymphocyte physiology
- CNS-infiltrating mononuclear cells have impaired lytic activity LP- and VP2-transfected target cells in vitro (TMEV leader peptide and VP2 capsid protein), in contrast to effective lysis demonstrated by control cells

abnormal T cell activation
- mutants exhibit an elevation of antigen-specific CD8+ T and CD4+ T cells in the bone marrow, liver, and spleen following LCMV infection compared to wild-type mice

increased spleen red pulp amount
- by 10-12 days after LCMV infection, red pulp is expanded when compared to wild-type mice

abnormal macrophage activation involved in immune response
- hemophagocytic macrophages are seen in lymph node, spleen, liver and bone marrow tissues of LCMV infected mutants unlike in wild-type mice

pancytopenia
- unlike wild-type mice, mutants become pancytopenic by 10 days after LCMV infection
- in LMCV-infected mice

thrombocytopenia
- in LMCV-infected mice

decreased erythrocyte cell number
- in LCMV-infected mice

homeostasis/metabolism phenotype

abnormal body temperature homeostasis
- while wild-type mice infected with LCMV develop a brief febrile response early after infection, mutants exhibit a prolonged temperature elevation that is still seen at 10 days after infection

increased circulating interleukin-1 beta level
- in LCMV-infected mice

increased circulating interleukin-6 level
- in LCMV-infected mice
- increased at 12 days after LCMV infection compared to wild-type mice
- in LMCV-infected mice

increased circulating lactate dehydrogenase level
- in LCMV-infected mice

increased circulating triglyceride level
- 8-10 days after LCMV infection, mutants develop hypertriglyceridemia compared to wild-type controls

decreased body temperature
- in LCMV-infected mice

increased circulating interferon-gamma level
- in LMCV-infected mice
- mutants exhibit elevated (10- to 100-fold) and prolonged serum levels of IFN-gamma following LCMV infection compared to wild-type mice
- mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias
- in LCMV-infected mice

abnormal circulating cytokine level

decreased circulating fibrinogen level
- 8-10 days after LCMV infection, mutants develop hypofibrinogenemia compared to wild-type controls

increased circulating aspartate transaminase level
- in LCMV-infected mice

increased circulating interleukin-10 level
- increased at 12 days after LCMV infection compared to wild-type mice

increased circulating interferon-alpha level
- mutants exhibit elevated serum levels of IFN-alpha at 6-8 days after LCMV infection unlike wild-type mice which show peak IFN-alpha levels at day 3 of infection and undetectable levels by 4-5 days of infection

increased circulating tumor necrosis factor level
- increased at 12 days after LCMV infection compared to wild-type mice
- in LCMV-infected mice

abnormal circulating fibrinogen level
- 8-10 days after LCMV infection, mutants develop hypofibrinogenemia compared to wild-type controls

increased circulating interleukin-18 level
- increased at 12 days after LCMV infection compared to wild-type mice

immune system phenotype

abnormal circulating fibrinogen level
- 8-10 days after LCMV infection, mutants develop hypofibrinogenemia compared to wild-type controls

decreased cytotoxic T cell cytolysis
- 2Ics cells
- reduced killing of anti-CD3-loaded P815 target cells, more pronounced than in than in Rab27a^ash and Stx11^tm1.2Ics cells

decreased interferon-gamma secretion
- IFN-gamma production by CD8+ T cells is less on a per-cell basis in response to both peptide and anti-CD3 stimulation after LCMV infection compared with wild-type mice, however the number of spontaneously IFN-gamma producing (without stimulation) CD8+ T cells is increased, indicating that ongoing antigenic stimulation results in the increased cytokine secretion
- ells is increased, indicating that ongoing antigenic stimulation results in the increased cytokine secretion

increased susceptibility to Picornaviridae infection
- at 45 days, viral mRNA is still detected in spinal cords of mutants but not in controls or Fas and Fasl mutants
- inflammation and tissue damage in the brain are greater than in control, resistant mice at 45 and 180 days

increased susceptibility to Riboviria infection
- LCMV-infected mice develop more severe hemophagocytic lymphohistiocytosis than in Rab27a^ash and Stx11^tm1.2Ics homozygotes despite similar viral loads
- LCMV-infected mice develop clinical features of hemophagocytic lymphohistiocytosis including weight loss, body temperature drop, hunched posture, lethargy, pancytopenia, lack of neutrophilia, increased circulating aspartate transaminase level, increased circulating lactate dehydrogenase level, increased serum levels of IFN-gamma, IL1b, TNF-alpha and IL6, increased viral load and worsening condition compared with wild-type mice
- mutants cannot clear lymphocytic choriomeningitic virus (LCMV) infection like wild-type mice can

increased susceptibility to viral infection
- LMCV-infected mice develop more severe hemophagocytic lymphohistiocytosis than in Rab27a^ash and Stx11^tm1.2Ics homozygotes despite similar viral loads
- at 45 days, viral mRNA is still detected in spinal cords of mutants but not in controls or Fas and Fasl mutants
- LMCV-infected mice develop clinical features of hemophagocytic lymphohistiocytosis including weight loss, body temperature drop, hunched posture, lethargy, pancytopenia, lack of neutrophilia, increased circulating aspartate transaminase level, increased circulating lactate dehydrogenase level, increased serum levels of IFN-gamma, IL1b, TNF-alpha and IL6, increased viral load and worsening condition compared with wild-type mice
- irculating lactate dehydrogenase level, increased serum levels of IFN-gamma, IL1b, TNF-alpha and IL6, increased viral load and worsening condition compared with wild-type mice
- mutants cannot clear lymphocytic choriomeningitic virus (LCMV) infection like wild-type mice can
- inflammation and tissue damage in the brain are greater than in control, resistant mice at 45 and 180 days
- homozygotes despite similar viral loads

brain inflammation
- by 45 days, inflammation with parenchymal disease is seen in hippocampus, striatum, and corpus callosum in some mice
- persistent inflammation is found in the brainstem of mutants
- 30 days after LCMV infection, the meninges show prominent mononuclear infiltrates along the dura
- at 180 days, brain pathology is still present
- by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6)

CNS inflammation
- by 21 days, inflammation with macrophage infiltration persists in the gray matter in mutants but not in controls
- by 7 days after TMEV infection, inflammation is present in the meninges and gray matter of spinal cords in controls as well

increased circulating interleukin-6 level
- in LCMV-infected mice
- increased at 12 days after LCMV infection compared to wild-type mice
- in LMCV-infected mice

increased susceptibility to viral infection induced morbidity/mortality
- mutants die within 2 weeks of lymphocytic choriomeningitic virus (LCMV) infection unlike wild-type mice
- mice die 2 weeks after LCMV infection
- neutralizing multiple cytokines, including TNF-alpha, IL-12, IL-18, M-CSF, and GM-CSF, with neutralizing antibodies has no effect on survival
- mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias
- mutants depleted of CD8+ cells (by administration of antibodies against CD8+ cells) survive LCMV infection, however those depleted of CD4+ or NK cells do not survive

decreased circulating fibrinogen level
- 8-10 days after LCMV infection, mutants develop hypofibrinogenemia compared to wild-type controls

increased circulating interferon-gamma level
- mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias
- in LMCV-infected mice
- in LCMV-infected mice
- mutants exhibit elevated (10- to 100-fold) and prolonged serum levels of IFN-gamma following LCMV infection compared to wild-type mice

increased susceptibility to Riboviria infection induced morbidity/mortality
- mutants die within 2 weeks of lymphocytic choriomeningitic virus (LCMV) infection unlike wild-type mice
- mutants depleted of CD8+ cells (by administration of antibodies against CD8+ cells) survive LCMV infection, however those depleted of CD4+ or NK cells do not survive
- mutants treated with neutralizing antibodies against IFN-gamma survive LCMV infection, do not develop histocytic infiltrates or peripheral blood cytopenias
- neutralizing multiple cytokines, including TNF-alpha, IL-12, IL-18, M-CSF, and GM-CSF, with neutralizing antibodies has no effect on survival

abnormal circulating cytokine level

abnormal spleen white pulp morphology
- by 10-12 days after LCMV infection, the white pulp appears chaotic with a prominent infiltrate of macrophages and activated lymphocytes when compared to wild-type spleen

increased circulating interleukin-1 beta level
- in LCMV-infected mice

lymph node inflammation
- by 10-12 days after LCMV infection, lymph node architecture is deranged with disorganized macrophage and activated lymphocyte infiltrates replacing the normal follicular structure

abnormal cytotoxic T cell physiology
- impaired CD8+ T cell degranulation
- Normal - however, priming is normal

abnormal lymph node morphology
- by 10-12 days after LCMV infection, lymph node architecture is deranged with disorganized macrophage and activated lymphocyte infiltrates replacing the normal follicular structure of lymph nodes

lymph node necrosis
- by 10-12 days after LCMV infection, some lymph nodes exhibit necrotic changes compared to wild-type mice

abnormal lymphocyte physiology
- CNS-infiltrating mononuclear cells have impaired lytic activity LP- and VP2-transfected target cells in vitro (TMEV leader peptide and VP2 capsid protein), in contrast to effective lysis demonstrated by control cells

abnormal macrophage activation involved in immune response
- hemophagocytic macrophages are seen in lymph node, spleen, liver and bone marrow tissues of LCMV infected mutants unlike in wild-type mice

decreased neutrophil cell number
- lack of neutrophilia in LCMV-infected mice

increased circulating interleukin-10 level
- increased at 12 days after LCMV infection compared to wild-type mice

increased circulating tumor necrosis factor level
- increased at 12 days after LCMV infection compared to wild-type mice
- in LCMV-infected mice

increased spleen red pulp amount
- by 10-12 days after LCMV infection, red pulp is expanded when compared to wild-type mice

decreased leukocyte cell number
- in LCMV-infected mice

decreased NK cell degranulation
- in the presence of recombinant IL15 alone or in combination with IL2

increased circulating interferon-alpha level
- mutants exhibit elevated serum levels of IFN-alpha at 6-8 days after LCMV infection unlike wild-type mice which show peak IFN-alpha levels at day 3 of infection and undetectable levels by 4-5 days of infection

abnormal T cell activation
- mutants exhibit an elevation of antigen-specific CD8+ T and CD4+ T cells in the bone marrow, liver, and spleen following LCMV infection compared to wild-type mice

increased circulating interleukin-18 level
- increased at 12 days after LCMV infection compared to wild-type mice

liver inflammation
- by 10-12 days after LCMV infection, livers show prominent periportal infiltrates

cellular phenotype

lymph node necrosis
- by 10-12 days after LCMV infection, some lymph nodes exhibit necrotic changes compared to wild-type mice

growth/size/body region phenotype

weight loss
- in LMCV-infected mice

References

Kagi D; Ledermann B; Burki K; Seiler P; Odermatt B; Olsen KJ; Podack ER; Zinkernagel RM; Hengartner H. 1994. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice [see comments] Nature 369(6475):31-7PubMed: 8164737 MGI: J:17986

Additional References

Chang E; Galle L; Maggs D; Estes DM; Mitchell WJ. 2000. Pathogenesis of herpes simplex virus type 1-induced corneal inflammation in perforin-deficient mice J Virol 74(24):11832-40PubMed: 11090183 MGI: J:65895
Choy JC; Kerjner A; Wong BW; McManus BM; Granville DJ. 2004. Perforin mediates endothelial cell death and resultant transplant vascular disease in cardiac allografts. Am J Pathol 165(1):127-33PubMed: 15215168 MGI: J:91236
Christensen JE; Wodarz D; Christensen JP; Thomsen AR. 2004. Perforin and IFN-gamma do not significantly regulate the virus-specific CD8+ T cell response in the absence of antiviral effector activity. Eur J Immunol 34(5):1389-94PubMed: 15114672 MGI: J:89390
Ledermann B; Burki K. 1991. Establishment of a germ-line competent C57BL/6 embryonic stem cell line. Exp Cell Res 197(2):254-8PubMed: 1959560 MGI: J:2753
Majlessi L; Bordenave G. 2001. Role of CD40 in a T cell-mediated negative regulation of Ig production. J Immunol 166(2):841-7PubMed: 11145658 MGI: J:88840
Murphy EA; Sathiyaseelan J; Parent MA; Zou B; Baldwin CL. 2001. Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice. Immunology 103(4):511-8PubMed: 11529943 MGI: J:71148
Takeda K; Hayakawa Y; Van Kaer L; Matsuda H; Yagita H; Okumura K. 2000. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci U S A 97(10):5498-503PubMed: 10792025 MGI: J:62215
Zhou P; Freidag BL; Caldwell CC; Seder RA. 2001. Perforin is required for primary immunity to Histoplasma capsulatum. J Immunol 166(3):1968-74PubMed: 11160245 MGI: J:67094

Additional - Prf1^tm1Sdz related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Prf1
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is a good breeder.

This colony is maintained by breeding homozygous siblings; reproduction performance is similar to C57LB/6J. Young mutants are susceptible to mouse hepatitis virus, but after reaching about eight weeks of age, they survive well conventional animal housing conditions. The expected coat color from breeding is black.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the Prf1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002407 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX27 (Maximum)

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Frozen Mouse Embryo	C57BL/6-Prf1<tm1Sdz>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6-Prf1<tm1Sdz>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6-Prf1<tm1Sdz>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	C57BL/6-Prf1<tm1Sdz>/J Frozen Embryos	$3373.50

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Prf1 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Prf1tm1Sdz

Allele Symbol: Prf1tm1Sdz

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Prf1tm1Sdz related

Mammalian Phenotype Terms by Genotype

Genotype: Prf1tm1Sdz/Prf1tm1SdzC.B6-Prf1

endocrine/exocrine gland phenotype

respiratory system phenotype

neoplasm

Genotype: Prf1tm1Sdz/Prf1+A.B6-Prf1

hematopoietic system phenotype

immune system phenotype

neoplasm

Genotype: Prf1tm1Sdz/Prf1tm1SdzA.B6-Prf1

hematopoietic system phenotype

immune system phenotype

neoplasm

Genotype: Prf1tm1Sdz/Prf1tm1Sdzinvolves: BALB/c * C57BL/6

hematopoietic system phenotype

immune system phenotype

Genotype: Prf1tm1Sdz/Prf1tm1SdzC57BL/6-Prf1

mortality/aging

hematopoietic system phenotype

neoplasm

reproductive system phenotype

immune system phenotype

Genotype: Prf1tm1Sdz/Prf1tm1SdzC57BL/6-Prf1/J

behavior/neurological phenotype

integument phenotype

liver/biliary system phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

cellular phenotype

growth/size/body region phenotype

References

Additional References

Additional - Prf1tm1Sdz related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

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Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Prf1^tm1Sdz

Allele Symbol: Prf1^tm1Sdz

Genotype: Prf1^tm1Sdz related

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
C.B6-Prf1

Genotype: Prf1^tm1Sdz/Prf1⁺
A.B6-Prf1

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
A.B6-Prf1

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
involves: BALB/c * C57BL/6

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
C57BL/6-Prf1

Genotype: Prf1^tm1Sdz/Prf1^tm1Sdz
C57BL/6-Prf1/J

Additional - Prf1^tm1Sdz related