Phenotypes associated with this allele

• Allele Symbol: Tg(tetO/CMV-Tslp)#Sfz
• Allele Name: transgene insertion, Steven F Ziegler
• Allele ID: MGI:5317863
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(KRT5-rtTA)1Glk/0 Tg(tetO/CMV-Tslp)#Sfz/0	C.Cg-Tg(KRT5-rtTA)1Glk Tg(tetO/CMV-Tslp)#Sfz	MGI:5317912
cx2	Tcrb^tm1Mom/Tcrb^tm1Mom Tg(KRT5-rtTA)1Glk/0 Tg(tetO/CMV-Tslp)#Sfz/0	involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N	MGI:5317870
cx3	Tg(KRT5-rtTA)1Glk/0 Tg(tetO/CMV-Tslp)#Sfz/0	involves: C3H * C57BL/6 * FVB/N	MGI:5317865
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	MGI:5503059

Genotype
MGI:5317912

cx1

• Allelic Composition: Tg(KRT5-rtTA)1Glk/0; Tg(tetO/CMV-Tslp)#Sfz/0
• Genetic Background: C.Cg-Tg(KRT5-rtTA)1Glk Tg(tetO/CMV-Tslp)#Sfz

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

immune system

increased susceptibility to autoimmune hemolytic anemia ( J:182756 )

• dox treated mutants develop autoimmune hemolytic anemia

abnormal B cell activation ( J:182756 )

• 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

increased B cell proliferation ( J:182756 )

• 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

increased circulating interleukin-4 level ( J:182756 )

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

increased autoantibody level ( J:182756 )

• following dox treatment, mutants show the presence of anti-RBC-specific autoantibodies

hematopoietic system

increased susceptibility to autoimmune hemolytic anemia ( J:182756 )

• dox treated mutants develop autoimmune hemolytic anemia

decreased hematocrit ( J:182756 )

• following dox treatment, mutants show a decrease in hematocrit corresponding with the presence of anti-RBC-specific autoantibodies, consistent with onset of hemolytic anemia

abnormal B cell activation ( J:182756 )

• 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

increased B cell proliferation ( J:182756 )

• 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

homeostasis/metabolism

increased circulating interleukin-4 level ( J:182756 )

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

cellular

increased B cell proliferation ( J:182756 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autoimmune hemolytic anemia		DOID:718	OMIM:205700	J:182756

Genotype
MGI:5317870

cx2

• Allelic Composition: Tcrb^tm1Mom/Tcrb^tm1Mom; Tg(KRT5-rtTA)1Glk/0; Tg(tetO/CMV-Tslp)#Sfz/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * FVB/N

integument

skin inflammation ( J:100506 )

• mutants treated with dox for 3 weeks exhibit dermal infiltration mostly of mast cells and eosinophils

abnormal dermal layer morphology ( J:100506 )

• mutants treated with doxycycline (dox) for 3 weeks exhibit dermal infiltration mostly of mast cells and eosinophils

thick epidermis ( J:100506 )

• mutants treated with dox for 3 weeks exhibit epidermal thickening

immune system

decreased IgE level ( J:100506 )

• dox treated mice exhibit little or no serum IgE

skin inflammation ( J:100506 )

• mutants treated with dox for 3 weeks exhibit dermal infiltration mostly of mast cells and eosinophils

hematopoietic system

decreased IgE level ( J:100506 )

• dox treated mice exhibit little or no serum IgE

Genotype
MGI:5317865

cx3

• Allelic Composition: Tg(KRT5-rtTA)1Glk/0; Tg(tetO/CMV-Tslp)#Sfz/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

integument

epidermal spongiosis ( J:100506 )

• by 5 weeks of doxycycline (dox) treatment, lesional skin shows characteristic changes of eczematous inflammation including spongiosis

dermatitis ( J:100506 )

• 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

hyperkeratosis ( J:100506 )

• by 5 weeks of dox treatment, lesional skin shows characteristic changes of eczematous inflammation including hyperkeratosis

acanthosis ( J:100506 )

• by 5 weeks of dox treatment, lesional skin shows characteristic changes of eczematous inflammation including acanthosis

dry skin ( J:100506 )

• majority of dox treated mice exhibit a mild xerosis

reddish skin ( J:100506 )

• seen in dox treated mutants

skin lesions ( J:100506 )

• 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

enlarged spleen ( J:100506 )

• dox treated mutants exhibit splenomegaly

increased CD4-positive, alpha-beta T cell number ( J:100506 )

• 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

increased IgE level ( J:100506 )

• in dox treated mutants

increased IgG1 level ( J:100506 )

• in dox treated mutants

decreased IgG2a level ( J:100506 )

• in dox treated mutants

abnormal cytokine level ( J:100506 )

• dox treated mutants exhibit an increase in Th2 cytokines in effected skin

abnormal lymph node morphology ( J:100506 )

• 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

enlarged lymph nodes ( J:100506 )

• dox treated mutants exhibit lymphadenopathy

conjunctivitis ( J:100506 )

• a few dox treated mice exhibit conjunctivitis

dermatitis ( J:100506 )

• 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

enlarged spleen ( J:100506 )

• dox treated mutants exhibit splenomegaly

increased CD4-positive, alpha-beta T cell number ( J:100506 )

• 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

increased IgE level ( J:100506 )

• in dox treated mutants

increased IgG1 level ( J:100506 )

• in dox treated mutants

decreased IgG2a level ( J:100506 )

• in dox treated mutants

homeostasis/metabolism

epidermal spongiosis ( J:100506 )

• by 5 weeks of doxycycline (dox) treatment, lesional skin shows characteristic changes of eczematous inflammation including spongiosis

abnormal cytokine level ( J:100506 )

• dox treated mutants exhibit an increase in Th2 cytokines in effected skin

vision/eye

conjunctivitis ( J:100506 )

• a few dox treated mice exhibit conjunctivitis

growth/size/body

enlarged spleen ( J:100506 )

• dox treated mutants exhibit splenomegaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:100506

Genotype
MGI:5503059

cx4

• Allelic Composition: Tg(KRT5-rtTA)1Glk/0; Tg(tetO-Tfrc/EGFP/Ova)#Sfz/0; Tg(tetO/CMV-Tslp)#Sfz/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

immune system

increased T cell proliferation ( J:199558 )

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

respiratory system inflammation ( J:199558 )

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

skin inflammation ( J:199558 )

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

integument

skin inflammation ( J:199558 )

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

respiratory system

respiratory system inflammation ( J:199558 )

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

hematopoietic system

increased T cell proliferation ( J:199558 )

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

cellular

increased T cell proliferation ( J:199558 )

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