Phenotypes Associated with This Genotype

Genotype
MGI:5563662

• Allelic Composition: Tg(KRT14-CASP1)1Miz/0
• Genetic Background: involves: C57BL/6

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

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:79706 )

• more than 80% of mice die within 6 days after Propionibacterium acnes administration compared to none of wild-type mice

growth/size/body

decreased body size ( J:79706 )

integument

increased keratinocyte apoptosis ( J:79706 )

• keratinocytes in the lesions show eosinophilic necrosis with nuclear condensation, indicating apoptosis

skin edema ( J:78602 )

• mice eventually develop papillomatosis with intercellular edema

dermatitis ( J:78602 , J:79706 )

• severe erosive dermatitis is seen at 8 weeks of age, followed by reepithalization and lichenoid changes (J:78602)

• mast cell number is increased in the dermal infiltrates (J:78602)

• mice exhibit chronic active dermatitis at 8 weeks of age from 8 weeks of age, mice develop focal dermatitis around their eyes, which rapidly develops into severe erosive dermatitis and extends onto face, ear, neck, neck, trunk, and legs within a few weeks (J:79706)

• dermis of ulcers is characterized by infiltration of many mononuclear cells (J:79706)

focal hair loss ( J:79706 )

• loss of facial hair and extremity hair is seen by 16 weeks of age

abnormal dermis papillary layer morphology ( J:78602 )

• mice eventually develop papillomatosis with intercellular edema

parakeratosis ( J:78602 , J:79706 )

• mice eventually exhibit parakeratotic scale-crust in the epidermis (J:78602)

• seen by 10 weeks of age (J:79706)

acanthosis ( J:78602 )

• mice eventually develop prominent acanthosis

skin lesions ( J:78602 )

• mice develop inflammatory skin lesion with high concentration of IgE

spontaneous skin ulceration ( J:79706 )

• after 16 weeks of age, multiple skin ulcers form and the ear and eyelids are deformed

• occasional skin ulcers are seen at 8 weeks of age and although reepithalization occurs, erosion occurs and ulcers relapse

psoriasis ( J:79706 )

• thick epidermis around ulcers at 10 weeks of age shows psoriasis-like changes including parakeratosis

immune system

increased neutrophil cell number ( J:78602 )

• proportion of neutrophils, as determined by Gr-1+ Mac-1+ cells, is elevated in the spleen

decreased T cell number ( J:78602 )

• splenic lymphocytes show a lower proportion of T cells compared to wild-type mice

increased IgE level ( J:78602 )

increased IgG1 level ( J:78602 )

abnormal T cell physiology ( J:78602 )

• isolated CD4+ T cells produce more IL-3, Il-4, and IL-5, but less IFN-gamma, in response to immobilized anti-CD3, compared to wild-type mice

increased circulating interleukin-18 level ( J:78602 , J:79706 )

• high concentration of IL-18 in the circulation at 4 weeks after birth, that gradually increases with growth (J:79706)

dermatitis ( J:78602 , J:79706 )

• severe erosive dermatitis is seen at 8 weeks of age, followed by reepithalization and lichenoid changes (J:78602)

• mast cell number is increased in the dermal infiltrates (J:78602)

• mice exhibit chronic active dermatitis at 8 weeks of age from 8 weeks of age, mice develop focal dermatitis around their eyes, which rapidly develops into severe erosive dermatitis and extends onto face, ear, neck, neck, trunk, and legs within a few weeks (J:79706)

• dermis of ulcers is characterized by infiltration of many mononuclear cells (J:79706)

increased susceptibility to bacterial infection ( J:79706 )

• P. acnes treated mice develop fatal hepatitis and show an increase in IFN-gamma levels following P. acnes infection that peaks at 4 days after infection that is not seen in wild-type mice

• treatment with a neutralizing anti-IL18 antibody completely rescues mice from fatal liver injury

• susceptibility to P. acnes induced liver injury is not different before and after the onset of skin changes

increased susceptibility to bacterial infection induced morbidity/mortality ( J:79706 )

• more than 80% of mice die within 6 days after Propionibacterium acnes administration compared to none of wild-type mice

homeostasis/metabolism

increased circulating histamine level ( J:78602 )

• elevation of plasma histamine levels

increased circulating interleukin-18 level ( J:78602 , J:79706 )

• high concentration of IL-18 in the circulation at 4 weeks after birth, that gradually increases with growth (J:79706)

skin edema ( J:78602 )

• mice eventually develop papillomatosis with intercellular edema

cellular

increased keratinocyte apoptosis ( J:79706 )

• keratinocytes in the lesions show eosinophilic necrosis with nuclear condensation, indicating apoptosis

behavior/neurological

excessive scratching ( J:78602 )

• mice frequently scratch their skin, particularly the skin lesion

hematopoietic system

increased neutrophil cell number ( J:78602 )

• proportion of neutrophils, as determined by Gr-1+ Mac-1+ cells, is elevated in the spleen

decreased T cell number ( J:78602 )

• splenic lymphocytes show a lower proportion of T cells compared to wild-type mice

increased IgE level ( J:78602 )

increased IgG1 level ( J:78602 )

abnormal T cell physiology ( J:78602 )

• isolated CD4+ T cells produce more IL-3, Il-4, and IL-5, but less IFN-gamma, in response to immobilized anti-CD3, compared to wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:78602