Phenotypes associated with this allele

• Allele Symbol: Il36g^tm1Lex
• Allele Name: targeted mutation 1, Lexicon Pharmaceuticals
• Allele ID: MGI:5007193
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il36g^tm1Lex/Il36g^tm1Lex	involves: 129S5/SvEvBrd	MGI:6467252
hm2	Il36g^tm1Lex/Il36g^tm1Lex	involves: 129S5/SvEvBrd * C57BL/6	MGI:6467324
hm3	Il36g^tm1Lex/Il36g^tm1Lex	involves: 129S5/SvEvBrd * C57BL/6J	MGI:6467014

Genotype
MGI:6467252

hm1

• Allelic Composition: Il36g^tm1Lex/Il36g^tm1Lex
• Genetic Background: involves: 129S5/SvEvBrd

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

mortality/aging

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:280917 )

• mice infected genitally with the Herpes simplex virus 2 (HSV-2 186) exhibit reduced survival time, succumbing to disease 2.6 days sooner than wild-type mice

immune system

decreased susceptibility to induced colitis ( J:256437 )

• mice treated with the hapten oxazolone to induce colitis (a TH2/9 model of colitis) show reduced weight loss and colonic inflammation compared to wild-type mice

decreased CD4-positive, alpha-beta T cell number ( J:256437 )

• following oxazolone-induced colitis, mice show reduced IL-9 producing CD4+ T cell frequency and absolute cell number indicating diminished TH9 cells

increased CD4-positive, alpha-beta T cell number ( J:256437 )

• following oxazolone-induced colitis, mice show an increase in the frequency and absolute number of Foxp3+CD4+ T cells in colonic tissue

increased regulatory T cell number ( J:256437 )

• following oxazolone-induced colitis, mice show increased frequency and absolute number of Helios-Foxp3+CD4+ T cells in colonic tissue indicating increased colonic T-reg cells

impaired neutrophil recruitment ( J:280917 )

• recruitment of mature neutrophils to the vaginal microenvironment is impaired in HSV-2-challened mice, with mice showing decreased numbers of CD11b+Ly6G+ neutrophils in vaginal lavages and lower neutrophil counts in vaginal tissue at 24 hours post HSV-2 infection

• however, macrophage or monocyte numbers in vaginal lavage after HSV-2 infection are not altered

decreased interleukin-9 secretion ( J:256437 )

• following oxazolone-induced colitis, mice show reduced IL-9 production by colonic lamina propria lymphocytes

increased susceptibility to Herpesvirales infection ( J:280917 )

• mice infected genitally with HSV-2 exhibit more rapid disease symptoms compared to wild-type mice, developing hair loss and erythema around the introitus 2.5 days earlier than controls

• mice exhibit delayed clearance of virus from the vaginal epithelium following HSV-2 infection, still showing titers at 6 dpi

• HSV-2 viral titers are detected in the brain stem, spinal cord, distal colon, and bladder, indicating increased systemic spread

increased susceptibility to Herpesvirales infection induced morbidity/mortality ( J:280917 )

• mice infected genitally with the Herpes simplex virus 2 (HSV-2 186) exhibit reduced survival time, succumbing to disease 2.6 days sooner than wild-type mice

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:256437 )

• following oxazolone-induced colitis, mice show reduced IL-9 producing CD4+ T cell frequency and absolute cell number indicating diminished TH9 cells

increased CD4-positive, alpha-beta T cell number ( J:256437 )

• following oxazolone-induced colitis, mice show an increase in the frequency and absolute number of Foxp3+CD4+ T cells in colonic tissue

increased regulatory T cell number ( J:256437 )

• following oxazolone-induced colitis, mice show increased frequency and absolute number of Helios-Foxp3+CD4+ T cells in colonic tissue indicating increased colonic T-reg cells

impaired neutrophil recruitment ( J:280917 )

• recruitment of mature neutrophils to the vaginal microenvironment is impaired in HSV-2-challened mice, with mice showing decreased numbers of CD11b+Ly6G+ neutrophils in vaginal lavages and lower neutrophil counts in vaginal tissue at 24 hours post HSV-2 infection

• however, macrophage or monocyte numbers in vaginal lavage after HSV-2 infection are not altered

digestive/alimentary system

decreased susceptibility to induced colitis ( J:256437 )

• mice treated with the hapten oxazolone to induce colitis (a TH2/9 model of colitis) show reduced weight loss and colonic inflammation compared to wild-type mice

behavior/neurological

hindlimb paralysis ( J:280917 )

• mice infected genitally with HSV-2 exhibit an increased incidence of hindlimb paralysis, indicating HSV-2 spread to the CNS, with 81.5% of mice developing paralysis after lethal challenge compared to 16.7% of wild-type mice

Genotype
MGI:6467324

hm2

• Allelic Composition: Il36g^tm1Lex/Il36g^tm1Lex
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:296074 )

• mice infected with Streptococcus pneumoniae exhibit increased mortality, showing 64% mortality by 10 days compared to 27% mortality in wild-type controls

immune system

impaired macrophage phagocytosis ( J:296074 )

• bone marrow derived macrophages exhibit reduced phagocytosis when incubated with labeled Streptococcus pneumoniae

abnormal macrophage activation involved in immune response ( J:296074 )

• pulmonary macrophages from Streptococcus pneumoniae infected mice show reduced M1 macrophage activation

abnormal cytokine level ( J:296074 )

• Streptococcus pneumoniae-infected mice show reduced expression of the type 1 cytokines TNF-alpha and IP-10/CXCL10 at 4 and 24 hours post infection, of IL-23p19 and IL-17 at 24 hours after infection, and IL-12p40 and IFN-gamma at 48 hours after infection

• Klebsiella pneumoniae-infected mice show decreased IL-12, IL-23, and IFN-gamma in the BALF 48 hours post infection

• cytokine induction is abrogated in wild-type bone marrow-derived dendritic cells incubated with microparticles from mutant pulmonary macrophages

• S.pneumoniae challenged mice administered cell-free microparticles isolated from wild-type macrophages show restoration of type-1 cytokine expression to wild-type levels

increased susceptibility to bacterial infection ( J:296074 )

• mice challenged with intrathecal Streptococcus pneumoniae (serotype3, 6303) exhibit decreased lung bacterial clearance and increased bacterial dissemination, reduced local expression of type 1 cytokines and impaired lung macrophage M1 polarization

• mice challenged with intrathecal Klebsiella pneumoniae (strain 43816, serotype 2) exhibit impaired lung bacterial clearance and increased bacterial dissemination

• S.pneumoniae challenged mice administered cell-free microparticles isolated from wild-type macrophages show reduced lung viral load

• however, mice show normal alveolar leukocyte influx in response to S. pneumoniae infection

increased susceptibility to bacterial infection induced morbidity/mortality ( J:296074 )

• mice infected with Streptococcus pneumoniae exhibit increased mortality, showing 64% mortality by 10 days compared to 27% mortality in wild-type controls

homeostasis/metabolism

abnormal cytokine level ( J:296074 )

• Streptococcus pneumoniae-infected mice show reduced expression of the type 1 cytokines TNF-alpha and IP-10/CXCL10 at 4 and 24 hours post infection, of IL-23p19 and IL-17 at 24 hours after infection, and IL-12p40 and IFN-gamma at 48 hours after infection

• Klebsiella pneumoniae-infected mice show decreased IL-12, IL-23, and IFN-gamma in the BALF 48 hours post infection

• cytokine induction is abrogated in wild-type bone marrow-derived dendritic cells incubated with microparticles from mutant pulmonary macrophages

• S.pneumoniae challenged mice administered cell-free microparticles isolated from wild-type macrophages show restoration of type-1 cytokine expression to wild-type levels

hematopoietic system

impaired macrophage phagocytosis ( J:296074 )

• bone marrow derived macrophages exhibit reduced phagocytosis when incubated with labeled Streptococcus pneumoniae

abnormal macrophage activation involved in immune response ( J:296074 )

• pulmonary macrophages from Streptococcus pneumoniae infected mice show reduced M1 macrophage activation

cellular

impaired macrophage phagocytosis ( J:296074 )

• bone marrow derived macrophages exhibit reduced phagocytosis when incubated with labeled Streptococcus pneumoniae

Genotype
MGI:6467014

hm3

• Allelic Composition: Il36g^tm1Lex/Il36g^tm1Lex
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6J

mortality/aging

increased susceptibility to Orthomyxoviridae infection induced morbidity/mortality ( J:264077 )

• mice exhibit greater mortality following influenza A PR8 infection than wild-type mice

• mice infected with the less pathogenic H3N2 influenza A/HKx31 virus show greater mortality than wild-type mice

• mice receiving a transfer of wild-type alveolar macrophages show an increase in survival following influenza A infection

immune system

increased macrophage apoptosis ( J:264077 )

• alveolar macrophage frequency and numbers rapidly decline following influenza A x31 infection and this loss is associated with a rapid increase in macrophage apoptosis

increased CD11b-high dendritic cell number ( J:264077 )

• influenza A x31-infected mice show increased numbers of CD11b^hi dendritic cells at 3 dpi but not 6 dpi

abnormal macrophage morphology ( J:264077 )

• alveolar macrophages from naive mice are skewed toward an M2-like macrophage polarization

decreased alveolar macrophage number ( J:264077 )

• influenza A x31-infected mice show decreased number of alveolar macrophages at 3 and 6 dpi

abnormal interleukin level ( J:264077 )

• BAL fluid of mice infected with a high dose of influenza A x31 shows increased IL-6 levels, but not IFN-gamma, TNF, or IL-1alpha

abnormal tumor necrosis factor level ( J:264077 )

• BAL fluid of mice infected with a high dose of influenza A x31 shows increased IFN-beta levels

increased susceptibility to Orthomyxoviridae infection ( J:264077 )

• influenza A PR8 infected mice exhibit increased viral load 6 days post infection (dpi) and greater mortality than controls

• influenza A x31 infected mice exhibit increased viral load, increased weight loss, greater mortality, and more diffuse immune infiltrate around the bronchioles than wild-type mice

increased susceptibility to Orthomyxoviridae infection induced morbidity/mortality ( J:264077 )

• mice exhibit greater mortality following influenza A PR8 infection than wild-type mice

• mice infected with the less pathogenic H3N2 influenza A/HKx31 virus show greater mortality than wild-type mice

• mice receiving a transfer of wild-type alveolar macrophages show an increase in survival following influenza A infection

growth/size/body

increased susceptibility to weight loss ( J:264077 )

• mice infected with influenza A x31 show increased weight loss beginning on day 3 post infection

hematopoietic system

increased macrophage apoptosis ( J:264077 )

• alveolar macrophage frequency and numbers rapidly decline following influenza A x31 infection and this loss is associated with a rapid increase in macrophage apoptosis

increased CD11b-high dendritic cell number ( J:264077 )

• influenza A x31-infected mice show increased numbers of CD11b^hi dendritic cells at 3 dpi but not 6 dpi

abnormal macrophage morphology ( J:264077 )

• alveolar macrophages from naive mice are skewed toward an M2-like macrophage polarization

decreased alveolar macrophage number ( J:264077 )

• influenza A x31-infected mice show decreased number of alveolar macrophages at 3 and 6 dpi

homeostasis/metabolism

abnormal interleukin level ( J:264077 )

• BAL fluid of mice infected with a high dose of influenza A x31 shows increased IL-6 levels, but not IFN-gamma, TNF, or IL-1alpha

abnormal tumor necrosis factor level ( J:264077 )

• BAL fluid of mice infected with a high dose of influenza A x31 shows increased IFN-beta levels

respiratory system

decreased alveolar macrophage number ( J:264077 )

• influenza A x31-infected mice show decreased number of alveolar macrophages at 3 and 6 dpi

cellular

increased macrophage apoptosis ( J:264077 )

• alveolar macrophage frequency and numbers rapidly decline following influenza A x31 infection and this loss is associated with a rapid increase in macrophage apoptosis