Mouse Genome Informatics
cx1
    Tg(KRT5-rtTA)1Glk/0
Tg(tetO/CMV-Tslp)#Sfz/0

C.Cg-Tg(KRT5-rtTA)1Glk Tg(tetO/CMV-Tslp)#Sfz
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mature follicular B cells in doxycycline (dox) treated mutants display features of polyclonal activation, including down-regulation of CD21/CD35 expression, elevated CD23 and MHC class II expression, increased cell size and increased mitogenic responses
• following polyclonal stimulation in vitro, primary B cells from dox treated mutants exhibit higher levels of [3H] thymidine incorporation, indicating increased proliferation potential
• following anti-IgM and LPS stimulation, primary B cells from dox treated mutants, exhibit higher levels of BrdU incorporation, indicating increased proliferation potential
• dox treated mutants develop autoimmune hemolytic anemia
• dox treated mutants exhibit an increase in serum IL-4 levels
• following dox treatment, mutants show the presence of anti-RBC-specific autoantibodies

hematopoietic system
• following dox treatment, mutants show a decrease in hematocrit corresponding with the presence of anti-RBC-specific autoantibodies, consistent with onset of hemolytic anemia
• mature follicular B cells in doxycycline (dox) treated mutants display features of polyclonal activation, including down-regulation of CD21/CD35 expression, elevated CD23 and MHC class II expression, increased cell size and increased mitogenic responses
• following polyclonal stimulation in vitro, primary B cells from dox treated mutants exhibit higher levels of [3H] thymidine incorporation, indicating increased proliferation potential
• following anti-IgM and LPS stimulation, primary B cells from dox treated mutants, exhibit higher levels of BrdU incorporation, indicating increased proliferation potential
• dox treated mutants develop autoimmune hemolytic anemia

homeostasis/metabolism
• dox treated mutants exhibit an increase in serum IL-4 levels

Mouse Models of Human Disease
OMIM IDRef(s)
Anemia, Autoimmune Hemolytic 205700 J:182756


Mouse Genome Informatics
cx2
    Tcrbtm1Mom/Tcrbtm1Mom
Tg(KRT5-rtTA)1Glk/0
Tg(tetO/CMV-Tslp)#Sfz/0

involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• mutants treated with dox for 3 weeks exhibit dermal infiltration mostly of mast cells and eosinophils
• mutants treated with doxycycline (dox) for 3 weeks exhibit dermal infiltration mostly of mast cells and eosinophils
• mutants treated with dox for 3 weeks exhibit epidermal thickening

immune system
• dox treated mice exhibit little or no serum IgE
• mutants treated with dox for 3 weeks exhibit dermal infiltration mostly of mast cells and eosinophils

hematopoietic system
• dox treated mice exhibit little or no serum IgE


Mouse Genome Informatics
cx3
    Tg(KRT5-rtTA)1Glk/0
Tg(tetO/CMV-Tslp)#Sfz/0

involves: C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• by 5 weeks of doxycycline (dox) treatment, lesional skin shows characteristic changes of eczematous inflammation including spongiosis
• mutants treated with doxycycline (dox) to induce expression of Tslp develop skin disease beginning at about 2-3 weeks of dox treatment
• dox treated mutants exhibit dermal infiltrates containing lymphocytes, macrophages, mast cells, and eosinophils
• however, inflammation is not seen in the small intestine or colon
• by 5 weeks of dox treatment, lesional skin shows characteristic changes of eczematous inflammation including hyperkeratosis
• by 5 weeks of dox treatment, lesional skin shows characteristic changes of eczematous inflammation including acanthosis
• majority of dox treated mice exhibit a mild xerosis
• seen in dox treated mutants
• dox treated mutants exhibit skin lesions consisting of mild erythema at 2 weeks of dox treatment with progression to eczematous-like changes, including erythema, crusting, and erosions, by 3-4 weeks of dox treatment
• skin lesions are most common on the snout, postauricular region, nape of the neck and upper back
• less commonly, lesions are seen on the anterior neck and hind legs

immune system
• dox treated mutants exhibit an increase in the frequency of and absolute numbers of IL-4 producing Th2 CD4+ T cells in both the spleens and lymph nodes
• dox treated mutants exhibit splenomegaly
• in dox treated mutants
• in dox treated mutants
• in dox treated mutants
• dox treated mutants exhibit an increase in Th2 cytokines in effected skin
• dox treated mutants exhibit a 14-fold increase in IL-4 producing cells in the skin-draining lymph nodes and an 18-fold increase in the intestinal mesenteric lymph nodes
• dox treated mutants exhibit lymphadenopathy
• a few dox treated mice exhibit conjunctivitis
• mutants treated with doxycycline (dox) to induce expression of Tslp develop skin disease beginning at about 2-3 weeks of dox treatment
• dox treated mutants exhibit dermal infiltrates containing lymphocytes, macrophages, mast cells, and eosinophils
• however, inflammation is not seen in the small intestine or colon

hematopoietic system
• dox treated mutants exhibit an increase in the frequency of and absolute numbers of IL-4 producing Th2 CD4+ T cells in both the spleens and lymph nodes
• dox treated mutants exhibit splenomegaly
• in dox treated mutants
• in dox treated mutants
• in dox treated mutants

homeostasis/metabolism
• by 5 weeks of doxycycline (dox) treatment, lesional skin shows characteristic changes of eczematous inflammation including spongiosis
• dox treated mutants exhibit an increase in Th2 cytokines in effected skin

vision/eye
• a few dox treated mice exhibit conjunctivitis

Mouse Models of Human Disease
OMIM IDRef(s)
Dermatitis, Atopic 603165 J:100506


Mouse Genome Informatics
cx4
    Tg(KRT5-rtTA)1Glk/0
Tg(tetO-Tfrc/EGFP/Ova)#Sfz/0
Tg(tetO/CMV-Tslp)#Sfz/0

involves: C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• of ovalbumin-specific CD4 T cells in doxycycline-treated mice unlike when cells are transferred into control mice
• airway inflammation in doxycycline-treated mice treated intranasally with ovalbumin
• eczematous inflammation in the skin of doxycycline- and anti-mTSLP antibody-treated mice

integument
• eczematous inflammation in the skin of doxycycline- and anti-mTSLP antibody-treated mice

respiratory system
• airway inflammation in doxycycline-treated mice treated intranasally with ovalbumin

hematopoietic system
• of ovalbumin-specific CD4 T cells in doxycycline-treated mice unlike when cells are transferred into control mice