Phenotypes Associated with This Genotype

Genotype
MGI:6330737

• Allelic Composition: Tg(KRT14-VP16/NR1I2)13Sdub/?
• Genetic Background: involves: C57BL/6

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

integument

increased keratinocyte proliferation ( J:258435 )

impaired skin barrier function ( J:258435 )

• 10-16 week old mice exhibit increased transepidermal water loss associated with increased skin surface pH

• the cutaneous barrier defect precedes the development of the Th2/Th17 skin immune response

skin inflammation ( J:258435 )

• mice exhibit Th2/Th17-mediated skin inflammation

• the cutaneous barrier defect precedes the development of the Th2/Th17 skin immune response

dermatitis ( J:258435 )

• skin microenvironment displays several key hallmarks of the immunological features seen in nonlesional atopic dermatitis

abnormal stratum corneum lipid matrix formation ( J:258435 )

• epidermis shows increased proportions of short-chain fatty acids (NS 24:0-26:0), increased content of the lysophosphatidylcholine species 16:0 and 18:0, the phsopatidylcholine species with C32 and C34, and long and very long chain sphingomyelin lipid species

epidermal hyperplasia ( J:258435 )

• skin exhibits mild-to-severe epidermal hyperplasia

thin epidermis ( J:258435 )

• slight, but significant, epidermal thinning at birth that is accentuated 5 days after birth

dry skin ( J:258435 )

• mice exhibit transient dry and scaly skin in the first days after birth

• however, mice do not exhibit gross skin abnormalities or scratching behavior at 10-16 weeks of age

scaly skin ( J:258435 )

• mice exhibit transient dry and scaly skin in the first days after birth

immune system

abnormal dendritic cell migration ( J:258435 )

• the migration of skin-derived dendritic cells is increased, particularly migration of Langerhans cells and Langerin- dermal dendritic cells

• however, the number of Langerin+ dermal dendritic cells are not changed and numbers of plasmacytoid dendritic cells are borderline increased in skin draining lymph nodes

increased dendritic cell number ( J:258435 )

• all populations of skin dendritic cells are increased

abnormal CD4-positive, alpha-beta T cell number ( J:258435 )

• both CD4+ and CD8+ T-cell populations are enlarged in the skin of mice, with a specific increase in dermal T cells

• percentages of IL-17A-producing alpha/beta dermal T lymphocytes are increased

increased effector memory T-helper cell number ( J:258435 )

• increase in numbers of effector memory T cells (in both the CD4+ and CD8+ subsets) in skin draining lymph nodes

increased leukocyte cell number ( J:258435 )

• proportions of CD45+ cells are increased in the skin and involve all leukocyte populations (lymphocytes, dendritic cells, and granulocytes such as eosinophils)

• peripheral blood shows increased percentages of leukocytes

increased gamma-delta T cell number ( J:258435 )

• percentages of IL-13-producing epidermal TCRgamma/delta+ T cells are enhanced in the skin

• peripheral blood shows increased percentages of TCRgamma/delta+ T cells and the percentage of IL-13-producing TCRgamma/delta+ T cells is enhanced in the blood

• however, IL-17A-producing gamma/delta T lymphocytes are not changed and production of IFN-gamma, IL-2,and IL-10 remains very low and unchanged in T lymphocytes

abnormal CD8-positive, alpha beta T cell morphology ( J:258435 )

• both CD4+ and CD8+ T-cell populations are enlarged in the skin of mice, with a specific increase in dermal T cells

increased IgE level ( J:258435 )

• increase in basal levels of serum IgE

increased IgG1 level ( J:258435 )

• 2.8-fold increase in levels of serum IgG1

enlarged lymph nodes ( J:258435 )

• mice have slightly enlarged skin draining lymph nodes containing increased numbers of lymphocytes and activated CD4+ and CD8+ lymphocytes

enhanced humoral immune response ( J:258435 )

• humoral Th2 immune response is triggered in the epidermis associated with increased serum IgE

decreased interleukin-1 beta secretion ( J:258435 )

• secretion of IL-1beta is abolished in keratinocytes

skin inflammation ( J:258435 )

• mice exhibit Th2/Th17-mediated skin inflammation

• the cutaneous barrier defect precedes the development of the Th2/Th17 skin immune response

dermatitis ( J:258435 )

• skin microenvironment displays several key hallmarks of the immunological features seen in nonlesional atopic dermatitis

abnormal innate immunity ( J:258435 )

• type 2 innate lymphoid cells are increased in the skin

homeostasis/metabolism

impaired skin barrier function ( J:258435 )

• 10-16 week old mice exhibit increased transepidermal water loss associated with increased skin surface pH

• the cutaneous barrier defect precedes the development of the Th2/Th17 skin immune response

abnormal pH regulation ( J:258435 )

• skin surface pH is increased

abnormal intercellular signaling peptide or protein level ( J:258435 )

• secretion of the growth factor GM-CSF is increased in keratinocytes

hematopoietic system

abnormal dendritic cell migration ( J:258435 )

• the migration of skin-derived dendritic cells is increased, particularly migration of Langerhans cells and Langerin- dermal dendritic cells

• however, the number of Langerin+ dermal dendritic cells are not changed and numbers of plasmacytoid dendritic cells are borderline increased in skin draining lymph nodes

increased dendritic cell number ( J:258435 )

• all populations of skin dendritic cells are increased

abnormal CD4-positive, alpha-beta T cell number ( J:258435 )

• both CD4+ and CD8+ T-cell populations are enlarged in the skin of mice, with a specific increase in dermal T cells

• percentages of IL-17A-producing alpha/beta dermal T lymphocytes are increased

increased effector memory T-helper cell number ( J:258435 )

• increase in numbers of effector memory T cells (in both the CD4+ and CD8+ subsets) in skin draining lymph nodes

increased leukocyte cell number ( J:258435 )

• proportions of CD45+ cells are increased in the skin and involve all leukocyte populations (lymphocytes, dendritic cells, and granulocytes such as eosinophils)

• peripheral blood shows increased percentages of leukocytes

increased gamma-delta T cell number ( J:258435 )

• percentages of IL-13-producing epidermal TCRgamma/delta+ T cells are enhanced in the skin

• peripheral blood shows increased percentages of TCRgamma/delta+ T cells and the percentage of IL-13-producing TCRgamma/delta+ T cells is enhanced in the blood

• however, IL-17A-producing gamma/delta T lymphocytes are not changed and production of IFN-gamma, IL-2,and IL-10 remains very low and unchanged in T lymphocytes

abnormal CD8-positive, alpha beta T cell morphology ( J:258435 )

• both CD4+ and CD8+ T-cell populations are enlarged in the skin of mice, with a specific increase in dermal T cells

increased IgE level ( J:258435 )

• increase in basal levels of serum IgE

increased IgG1 level ( J:258435 )

• 2.8-fold increase in levels of serum IgG1

cellular

abnormal dendritic cell migration ( J:258435 )

• the migration of skin-derived dendritic cells is increased, particularly migration of Langerhans cells and Langerin- dermal dendritic cells

• however, the number of Langerin+ dermal dendritic cells are not changed and numbers of plasmacytoid dendritic cells are borderline increased in skin draining lymph nodes

increased keratinocyte proliferation ( J:258435 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:258435