Phenotypes associated with this allele

• Allele Symbol: Prf1^tm1Clrk
• Allele Name: targeted mutation 1, William R Clark
• Allele ID: MGI:2158403
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Prf1^tm1Clrk/Prf1^tm1Clrk	C.129S7(B6)-Prf1^tm1Clrk	MGI:3529345
hm2	Prf1^tm1Clrk/Prf1^tm1Clrk	involves: 129S7/SvEvBrd * BALB/c * NOD	MGI:3622763
hm3	Prf1^tm1Clrk/Prf1^tm1Clrk	involves: 129S7/SvEvBrd * C57BL/6	MGI:3528063
cx4	Prf1^tm1Clrk/Prf1^tm1Clrk Tg(INS-Il10)#Sar/0	involves: 129S7/SvEvBrd * BALB/c * NOD	MGI:3622764

Genotype
MGI:3529345

hm1

• Allelic Composition: Prf1^tm1Clrk/Prf1^tm1Clrk
• Genetic Background: C.129S7(B6)-Prf1^tm1Clrk

• ♀: 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: Prf1^tm1Clrk/Prf1^tm1Clrk
• Genetic Background: involves: 129S7/SvEvBrd * BALB/c * NOD

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: Prf1^tm1Clrk/Prf1^tm1Clrk
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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: Prf1^tm1Clrk/Prf1^tm1Clrk; Tg(INS-Il10)#Sar/0
• Genetic Background: involves: 129S7/SvEvBrd * BALB/c * NOD

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