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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Prf1tm1Clrk
targeted mutation 1, William R Clark
MGI:2158403
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
 		Prf1tm1Clrk/Prf1tm1Clrk C.129S7(B6)-Prf1tm1Clrk MGI:3529345
hm2
 		Prf1tm1Clrk/Prf1tm1Clrk involves: 129S7/SvEvBrd * BALB/c * NOD MGI:3622763
hm3
 		Prf1tm1Clrk/Prf1tm1Clrk involves: 129S7/SvEvBrd * C57BL/6 MGI:3528063
cx4
 		Prf1tm1Clrk/Prf1tm1Clrk
Tg(INS-Il10)#Sar/0 		involves: 129S7/SvEvBrd * BALB/c * NOD MGI:3622764


Genotype
MGI:3529345
hm1
Allelic
Composition		 Prf1tm1Clrk/Prf1tm1Clrk
Genetic
Background		 C.129S7(B6)-Prf1tm1Clrk
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prf1tm1Clrk mutation (2 available); any Prf1 mutation (52 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:71576 )
N
• similar to wild-type, antiviral CTL from RSV-infected mutants are capable of lysing target cells by a perforin-independent, FasL-dependent mechanism that is inhibited by anti-FasL antibody
increased activated T cell number ( J:71576 )
• RSV-infected homozygotes show a significantly higher % of CD8+ T cells on day 8 post-infection relative to wild-type; no significant differences are noted in the lungs on days 4, 6, and 10
• consistent with increased CD8+ T cell numbers, mutants show enhanced lung histopathology on day 8 after RSV infection, with marked cellularity around the interstitial spaces
abnormal cytokine secretion ( J:71576 )
• antiviral cytokine production is temporally correlated with illness
increased interferon-gamma secretion ( J:71576 )
• RSV-infected mutants produce 5-fold more IFN-gamma on day 8 and 3-fold more on day 10 relative to wild-type mice
increased tumor necrosis factor secretion ( J:71576 )
• RSV-infected mutants produce 3-fold more TNF on day 8 relative to wild-type mice
increased susceptibility to Riboviria infection ( J:71576 )
• in response to respiratory syncytial virus (RSV) infection, homozygotes exhibit delayed virus clearance relative to wild-type
• RSV-infected mutants retain a higher titer of virus at days 6 and 8; however, both genotypes clear the virus by day 10, suggesting an alternative mode of RSV clearance
• homozygotes display a delay in RSV-induced weight loss and illness as well as a prolonged recovery relative to wild-type

hematopoietic system
increased activated T cell number ( J:71576 )
• RSV-infected homozygotes show a significantly higher % of CD8+ T cells on day 8 post-infection relative to wild-type; no significant differences are noted in the lungs on days 4, 6, and 10
• consistent with increased CD8+ T cell numbers, mutants show enhanced lung histopathology on day 8 after RSV infection, with marked cellularity around the interstitial spaces




Genotype
MGI:3622763
hm2
Allelic
Composition		 Prf1tm1Clrk/Prf1tm1Clrk
Genetic
Background		 involves: 129S7/SvEvBrd * BALB/c * NOD
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prf1tm1Clrk mutation (2 available); any Prf1 mutation (52 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
decreased susceptibility to autoimmune diabetes ( J:64051 )
• mice do not develop diabetes over 12 weeks while transgenic littermates all develop diabetes (blood glucose >300mg/dl) in the same period

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
type 1 diabetes mellitus DOID:9744 OMIM:222100
 J:64051




Genotype
MGI:3528063
hm3
Allelic
Composition		 Prf1tm1Clrk/Prf1tm1Clrk
Genetic
Background		 involves: 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prf1tm1Clrk mutation (2 available); any Prf1 mutation (52 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:21531 )
N
• when kept in an ultra clean room, homozygotes remain healthy with grossly normal lymphoid organs and tissues, and normal distribution of CD4+ and CD8+ T cell subsets in their spleens relative to wild-type mice
decreased cytotoxic T cell cytolysis ( J:21531 )
• in response to LCMV infection, mutant splenocytes show no detectable killing of LCMV-infected fibroblast target cells, despite adequate expansion and activation of CD8+ T cells
• following activation with PMA and ionomycin, splenocytes from LCMV-infected mutants are able to lyse hematopoietic target cells transfected with Fas sense cDNA, but not with Fas anti-sense cDNA; this lysis is not sensitive to EGTA
• in MLC reactions, both wild-type and mutant splenocytes respond to alloantigen by blastogenesis and proliferation; however, mutant cells lyse hematopoietic target cells less efficiently than wild-type cells, and only if targeted cells express Fas antigen
• lysis of Fas+ targets by mutant CTLs generated in primary MLC varies widely in its sensitivity to EGTA from almost completely sensitive to almost completely insensitive
• on the other hand, lysis by mutant CTL lines is generally insensitive to EGTA or is slightly enhanced by it
increased susceptibility to Riboviria infection ( J:21531 )
• in response to lymphocytic choriomeningitis virus (LCMV) infection, homozygotes fail to generate a robust anti-viral CTL reponse and are unable to clear the infection by day 8 post-infection, with signs of weight loss and increasing sickness over time
• by day 8, LCMV-infected homozygotes continue to harbor high levels of virus in all tissues and in serum, despite large numbers of cellular infiltrates containing CD8+ T cells

hematopoietic system
decreased cytotoxic T cell cytolysis ( J:21531 )
• in response to LCMV infection, mutant splenocytes show no detectable killing of LCMV-infected fibroblast target cells, despite adequate expansion and activation of CD8+ T cells
• following activation with PMA and ionomycin, splenocytes from LCMV-infected mutants are able to lyse hematopoietic target cells transfected with Fas sense cDNA, but not with Fas anti-sense cDNA; this lysis is not sensitive to EGTA
• in MLC reactions, both wild-type and mutant splenocytes respond to alloantigen by blastogenesis and proliferation; however, mutant cells lyse hematopoietic target cells less efficiently than wild-type cells, and only if targeted cells express Fas antigen
• lysis of Fas+ targets by mutant CTLs generated in primary MLC varies widely in its sensitivity to EGTA from almost completely sensitive to almost completely insensitive
• on the other hand, lysis by mutant CTL lines is generally insensitive to EGTA or is slightly enhanced by it




Genotype
MGI:3622764
cx4
Allelic
Composition		 Prf1tm1Clrk/Prf1tm1Clrk
Tg(INS-Il10)#Sar/0
Genetic
Background		 involves: 129S7/SvEvBrd * BALB/c * NOD
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prf1tm1Clrk mutation (2 available); any Prf1 mutation (52 available)
Tg(INS-Il10)#Sar mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
decreased susceptibility to autoimmune diabetes ( J:64051 )
• only 11% of animals develop diabetes by 5 weeks of age (blood glucose >300 mg/dl), while 50% of wild-type transgenic animals develop diabetes, but the overall incidence by 12 weeks is the same for both
• mice are considered diabetic after a blood glucose measure of >300 mg/dl

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
type 1 diabetes mellitus DOID:9744 OMIM:222100
 J:64051




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12/10/2024
MGI 6.24 		The Jackson Laboratory