Phenotypes Associated with This Genotype

Genotype
MGI:6241552

• Allelic Composition: Adam17^tm1.2Bbl/Adam17^tm1.2Bbl; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: B6.129(SJL)-Sox9^tm3(cre)Crm Adam17^tm1.2Bbl

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

integument

impaired skin barrier function ( J:229771 )

• increase in transepidermal water loss indicating barrier dysfunction

dermatitis ( J:229771 )

• dry skin progresses to eczematous lesion (eczematous dermatitis)

• skin lesions show mononuclear cell infiltrates including lymphocytes and mast cells

• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5^neg gammadelta TCR^mid T cells and CD4+ T cells

• about 20% of Vgamma5^neg gammadelta TCR^mid T cells express Vgamma4, but the majority do not

• analysis of infiltrating T cells shows that epidermal CD4 T cells consist of Th17 and Th22 cells, and the majority of Vgamma5^neg gammadelta TCR^mid T cells produce interleukin-17 (gammadeltaT17) and a fraction of which also produce interleukin-22

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning are almost completely protected from developing eczematous lesions, however skin inflammation develops upon antibiotic withdrawal

• mice treated with antibiotics at 10 weeks after birth show improvement in eczematous dermatitis and inflammation

abnormal skin morphology ( J:229771 )

• mice exhibit altered skin microbiota, with a striking overgrowth of S. aureus which is seen within stratum corneum and follicular openings

• skin microbiota undergoes a sequential change where dysbiosis starts with the emergence of Corynebacterium mastitidis and then S. aureus and Corynebacterium bovis predominating later

• antibiotic-treated mice exhibit a higher bacterial diversity, with a reduction in S. aureus and C. bovis, however, withdrawal of antibiotics leads to skin microbiome dysbiosis

• mice treated with antibiotics at 10 weeks after birth show reversal of skin microbiome dysbiosis

abnormal epidermal layer morphology ( J:229771 )

• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5^neg gammadelta TCR^mid T cells and CD4+ T cells

• antibiotic treatment normalizes epidermal gammadelta T cell constituents

• antibiotic treatment does not affect CD4+ T cell numbers in the epidermis and they remain high, however these T cells produce less IL-4 and do not produce IL-17A or IL-22

dry skin ( J:229771 )

• mice exhibit dry skin around 3 weeks after birth

increased pruritus ( J:229771 )

• mice develop intense pruritus

immune system

increased T-helper 1 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th1 cells

increased T-helper 17 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates a prominent increase in Th17 cells

• antibiotic treated mice show a reduction in the numbers of Th17 cells in skin draining lymph nodes

increased T-helper 2 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th2 cells

• antibiotic treated mice show a reduction in the numbers of Th2 cells in skin draining lymph nodes

increased IgE level ( J:229771 )

• serum IgE levels are elevated

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning have lower serum IgE concentrations

abnormal circulating chemokine level ( J:229771 )

• CCL17, a T helper 2 cell chemokine, levels are elevated

dermatitis ( J:229771 )

• dry skin progresses to eczematous lesion (eczematous dermatitis)

• skin lesions show mononuclear cell infiltrates including lymphocytes and mast cells

• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5^neg gammadelta TCR^mid T cells and CD4+ T cells

• about 20% of Vgamma5^neg gammadelta TCR^mid T cells express Vgamma4, but the majority do not

• analysis of infiltrating T cells shows that epidermal CD4 T cells consist of Th17 and Th22 cells, and the majority of Vgamma5^neg gammadelta TCR^mid T cells produce interleukin-17 (gammadeltaT17) and a fraction of which also produce interleukin-22

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning are almost completely protected from developing eczematous lesions, however skin inflammation develops upon antibiotic withdrawal

• mice treated with antibiotics at 10 weeks after birth show improvement in eczematous dermatitis and inflammation

hematopoietic system

increased T-helper 1 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th1 cells

increased T-helper 17 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates a prominent increase in Th17 cells

• antibiotic treated mice show a reduction in the numbers of Th17 cells in skin draining lymph nodes

increased T-helper 2 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th2 cells

• antibiotic treated mice show a reduction in the numbers of Th2 cells in skin draining lymph nodes

increased IgE level ( J:229771 )

• serum IgE levels are elevated

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning have lower serum IgE concentrations

homeostasis/metabolism

abnormal circulating chemokine level ( J:229771 )

• CCL17, a T helper 2 cell chemokine, levels are elevated

impaired skin barrier function ( J:229771 )

• increase in transepidermal water loss indicating barrier dysfunction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:229771