Phenotypes associated with this allele

• Allele Symbol: Irf1^tm1Mak
• Allele Name: targeted mutation 1, Tak Mak
• Allele ID: MGI:1857205
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Irf1^tm1Mak/Irf1^tm1Mak	B6.129S2-Irf1^tm1Mak/J	MGI:3769118
hm2	Irf1^tm1Mak/Irf1^tm1Mak	either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)	MGI:2180209
hm3	Irf1^tm1Mak/Irf1^tm1Mak	involves: 129S2/SvPas	MGI:3769119
hm4	Irf1^tm1Mak/Irf1^tm1Mak	involves: 129S2/SvPas * C57BL/6J	MGI:3769123
ht5	Irf1^tm1Mak/Irf1^+	either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)	MGI:3769111
cx6	Irf1^tm1Mak/Irf1^tm1Mak Miga2^tm1a(KOMP)Wtsi/Miga2^tm1a(KOMP)Wtsi	B6.Cg-Miga2^tm1a(KOMP)Wtsi Irf1^tm1Mak	MGI:7716957
cx7	Irf1^tm1Mak/Irf1^tm1Mak Tg(HRAS)2Jic/?	involves: 129S2/SvPas * BALB/c * C57BL/6	MGI:4819237
cx8	Irf1^tm1Mak/Irf1^tm1Mak Trp53^tm1Sia/Trp53^tm1Sia	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:4819238
cx9	Fas^lpr/Fas^lpr Irf1^tm1Mak/Irf1^+	MRL.Cg-Irf1^tm1Mak Fas^lpr	MGI:3769144
cx10	Fas^lpr/Fas^lpr Irf1^tm1Mak/Irf1^tm1Mak	MRL.Cg-Irf1^tm1Mak Fas^lpr	MGI:3769143

Genotype
MGI:3769118

hm1

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: B6.129S2-Irf1^tm1Mak/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:91927 )

• treatment with recombinant IL12 significantly improves survival of MNU treated mice

• increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls

homeostasis/metabolism

abnormal circulating alanine transaminase level ( J:111090 )

• when subjected to warm ischemia/reperfusion (I/R), 60 minutes of warm hepatic ischemia followed by 6 hours of reperfusion significantly increase serum ALT levels in controls, but levels in treated mutants are ~60% lower than I/R-treated wild-type mice

increased susceptibility to xenobiotic induced morbidity/mortality ( J:91927 )

• increase in mortality following a single dose of N-methyl-N-nitrosourea (MNU) compared to similarly treated wild-type controls

• treatment with recombinant IL12 significantly improves survival of MNU treated mice

increased incidence of tumors by chemical induction ( J:91927 )

• following a single dose of MNU most mice develop massive lymphoid neoplasias

• treatment with recombinant IL12 reduces the incidence of lymphomas in MNU treated mice

immune system

abnormal lymphocyte physiology ( J:91927 )

• impairment in the ability to produce IFNG in response to Con A stimulation

• IL12 treatment can rescue the impairment in IFNG production

decreased interferon-gamma secretion ( J:91927 )

• by lymphocytes following Con A stimulation

• IL12 treatment can rescue the impairment in IFNG production

neoplasm

increased incidence of tumors by chemical induction ( J:91927 )

• following a single dose of MNU most mice develop massive lymphoid neoplasias

• treatment with recombinant IL12 reduces the incidence of lymphomas in MNU treated mice

increased lymphoma incidence ( J:91927 )

• following a single dose of MNU compared to similarly treated wild-type controls

hematopoietic system

abnormal lymphocyte physiology ( J:91927 )

• impairment in the ability to produce IFNG in response to Con A stimulation

• IL12 treatment can rescue the impairment in IFNG production

Genotype
MGI:2180209

hm2

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

hematopoietic system

abnormal T cell number ( J:64286 )

• CD8+/CD4+ T cell ratio is lower than wild-type or Irf2-deficient mice during course of LCMV infection

increased double-positive T cell number ( J:64286 )

• numbers are normal or slightly increased in thymi

increased CD4-positive, alpha-beta T cell number ( J:64286 )

• CD4+CD8- T cells are often but not always increased in number in homozygotes

decreased CD8-positive, alpha-beta T cell number ( J:64286 )

• 10-fold reduction in TCR alpha-beta CD4-CD8+ T cells is observed in peripheral blood, spleen, thymus, and lymph nodes

immune system

immune system phenotype ( J:64286 )

N • humoral response to vesicular stomatitis virus challenge is normal; kinetics of immunoglobulin class switching and antibody levels are comparable to wild-type mice

abnormal T cell number ( J:64286 )

• CD8+/CD4+ T cell ratio is lower than wild-type or Irf2-deficient mice during course of LCMV infection

increased double-positive T cell number ( J:64286 )

• numbers are normal or slightly increased in thymi

increased CD4-positive, alpha-beta T cell number ( J:64286 )

• CD4+CD8- T cells are often but not always increased in number in homozygotes

decreased CD8-positive, alpha-beta T cell number ( J:64286 )

• 10-fold reduction in TCR alpha-beta CD4-CD8+ T cells is observed in peripheral blood, spleen, thymus, and lymph nodes

abnormal response to infection ( J:64286 )

• significantly reduced cytotoxic responses against LCMV-infected target cells are observed

Genotype
MGI:3769119

hm3

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: involves: 129S2/SvPas

cellular

cellular phenotype ( J:115104 )

N • apoptosis following UV-induced damage is similar in mutant primary hepatocytes from 6-10 week males and wild-type cells

N • 6-12 hours after UV irradiation, hepatocytes arrest in at G₁/S, similar to wild-type cells

abnormal DNA repair ( J:115104 )

• cultured hepatocytes from 6-10 week males show a defect in DNA repair in an assay in which repair of a UV-damaged reporter plasmid by wild-type and null hepatocytes; recovery of reporter activity by Irf1-deficient hepatocytes is significantly lower than that of wild-type or Trp53-deficient cells

homeostasis/metabolism

abnormal DNA repair ( J:115104 )

• cultured hepatocytes from 6-10 week males show a defect in DNA repair in an assay in which repair of a UV-damaged reporter plasmid by wild-type and null hepatocytes; recovery of reporter activity by Irf1-deficient hepatocytes is significantly lower than that of wild-type or Trp53-deficient cells

Genotype
MGI:3769123

hm4

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

cardiovascular system

abnormal vascular wound healing ( J:118512 )

• 28 days after induction of flow cessation in the common carotid artery, a significant increase of neointima formation was observed proximal of the ligation suture in mutants compared to control wild-type mice

homeostasis/metabolism

abnormal vascular wound healing ( J:118512 )

• 28 days after induction of flow cessation in the common carotid artery, a significant increase of neointima formation was observed proximal of the ligation suture in mutants compared to control wild-type mice

Genotype
MGI:3769111

ht5

• Allelic Composition: Irf1^tm1Mak/Irf1⁺
• Genetic Background: either: (involves: 129S2/SvPas * C57BL/6J) or (involves: 129S2/SvPas * C57BL/6J * DBA/2)

normal phenotype

no abnormal phenotype detected ( J:64286 )

• mice are viable and fertile, with no detectable abnormalities

Genotype
MGI:7716957

cx6

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak; Miga2^{tm1a(KOMP)Wtsi}/Miga2^{tm1a(KOMP)Wtsi}
• Genetic Background: B6.Cg-Miga2^{tm1a(KOMP)Wtsi} Irf1^tm1Mak

behavior/neurological

behavior/neurological phenotype ( J:339075 )

N • mice show restoration of most of the anxiety-like phenotypes seen in single Miga2^{tm1a(KOMP)Wtsi} homozygotes

Genotype
MGI:4819237

cx7

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak; Tg(HRAS)2Jic/?
• Genetic Background: involves: 129S2/SvPas * BALB/c * C57BL/6

neoplasm

increased tumor incidence ( J:55418 )

• 44% develop tumors as compared to 7% of controls

increased hemangiosarcoma incidence ( J:55418 )

• angiosarcomas observed most frequently

Genotype
MGI:4819238

cx8

• Allelic Composition: Irf1^tm1Mak/Irf1^tm1Mak; Trp53^tm1Sia/Trp53^tm1Sia
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CBA

mortality/aging

decreased tumor-free survival time ( J:55418 )

• earlier tumor induced death

neoplasm

increased tumor incidence ( J:55418 )

• 96% develop tumors by 299 days of age compared to 56% of mice only homozygous for Trp53^tm1Sia

• greater frequency of multiple tumors

increased lymphoma incidence ( J:55418 )

increased hemangiosarcoma incidence ( J:55418 )

• angiosarcoma

increased teratoma incidence ( J:55418 )

• immature teratomas

Genotype
MGI:3769144

cx9

• Allelic Composition: Fas^lpr/Fas^lpr; Irf1^tm1Mak/Irf1⁺
• Genetic Background: MRL.Cg-Irf1^tm1Mak Fas^lpr

mortality/aging

premature death ( J:114771 )

• 50% of mice die by 52 weeks; survival is increased relative to MRL-Fas^lpr mice

renal/urinary system

increased urine protein level ( J:114771 )

• not significantly different from Fas^lpr, Irf1-null mice or Fas^lpr, Irf1-sufficient mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• mice display similar T cell population profiles to Fas^lpr, Irf1-null mice

immune system

immune system phenotype ( J:114771 )

N • TNF alpha production is not significantly different Fas^lpr, Irf1-sufficient mice or Fas^lpr, Irf1-null mice

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• mice display similar T cell population profiles to Fas^lpr, Irf1-null mice

increased anti-double stranded DNA antibody level ( J:114771 )

• at 26 weeks of age, levels are significantly higher relative to Fas^lpr, Irf1-null mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

homeostasis/metabolism

increased urine protein level ( J:114771 )

• not significantly different from Fas^lpr, Irf1-null mice or Fas^lpr, Irf1-sufficient mice

integument

abnormal skin condition ( J:114771 )

• mice display varying severity of skin irritation ranging from little or none to mild or moderate to severe

Genotype
MGI:3769143

cx10

• Allelic Composition: Fas^lpr/Fas^lpr; Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: MRL.Cg-Irf1^tm1Mak Fas^lpr

mortality/aging

premature death ( J:114771 )

• 50% of mice die by 45 weeks; survival is increased relative to MRL-Fas^lpr mice

immune system

immune system phenotype ( J:114771 )

N • TNF alpha production is not significantly different from Fas^lpr, Irf1-sufficient mice

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• at 12 weeks, splenic CD4+CD25+ T cells are increased in percentage compared to wild-type MRL-Fas^lpr mice; percentage increases from 27.1% at 8 weeks to 40.3% at 26 weeks in wild-type mice, double mutants have 60.6% at 26 weeks

• 26 week old mice have a percentage of CD4+CD25+CD62L+ T cells (32.2%) compared to wild-type MRL-Fas^lpr mice (13.1%)

abnormal cytokine secretion ( J:114771 )

• mesangial cells from 8- and 26-week old mice show significantly less Il12 production than Fas^lpr, Irf1-sufficient cells upon stimulation with LPS and interferon gamma

decreased anti-double stranded DNA antibody level ( J:114771 )

• levels of anti-dsDNA IgG2a are significantly decreased relative to Fas^lpr, Irf1-sufficient mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• at 12 weeks, splenic CD4+CD25+ T cells are increased in percentage compared to wild-type MRL-Fas^lpr mice; percentage increases from 27.1% at 8 weeks to 40.3% at 26 weeks in wild-type mice, double mutants have 60.6% at 26 weeks

• 26 week old mice have a percentage of CD4+CD25+CD62L+ T cells (32.2%) compared to wild-type MRL-Fas^lpr mice (13.1%)

renal/urinary system

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:114771 )

N • only 1 mouse had abnormal urine protein levels (above 200 mg/dl) at 24 weeks of age

cellular

abnormal cell physiology ( J:114771 )

• in response to LPS + IFN gamma stimulation, mesangial cells show significantly lower activation than cells from MRL-Fas^lpr mice

integument

integument phenotype ( J:114771 )

N • mice do not show characteristic signs of skin disease; at 26 weeks of age, 7/10 mice show no skin involvement, while 3 show minimal skin irritation, compared to 8/10 Fas^lpr, Irf1 sufficient mice displaying moderate to severe skin involvement