Phenotypes Associated with This Genotype

Genotype
MGI:5583018

• Allelic Composition: Tg(IVL-KLK5)#Hov/0
• Genetic Background: involves: C57BL/6 * CBA

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

growth/size/body

decreased birth body size ( J:210758 )

• mice are slightly smaller at birth, however adult mice show normal size and body weight

postnatal growth retardation ( J:210758 )

• all mice show growth delay at 1 month of age

enlarged spleen ( J:210758 )

behavior/neurological

excessive scratching ( J:210758 )

• adult mice develop intense and continuous scratching resulting in chronic and extensive erosions and crusts

homeostasis/metabolism

abnormal circulating cytokine level ( J:210758 )

• serum levels of Tslp, a pro-Th2 cytokine, are elevated

impaired skin barrier function ( J:210758 )

• neonates show more patches of dye penetration on the neck, abdomen, muzzle, and ears, suggesting defective skin barrier

• neonates show higher transepidermal water loss than wild-type mice with a further increase at P8

abnormal enzyme/coenzyme activity ( J:210758 )

• increase in proteolytic activity in the epidermis and caseinolytic, elastinolytic, and gelatinolytic activities are increased in the dermis

integument

impaired skin barrier function ( J:210758 )

• neonates show more patches of dye penetration on the neck, abdomen, muzzle, and ears, suggesting defective skin barrier

• neonates show higher transepidermal water loss than wild-type mice with a further increase at P8

skin inflammation ( J:210758 )

• nonlesional skin shows infiltrates of T cells, mast cells and eosinophil granulocytes in the dermis

• nonlesional skin shows upregulation of chemokines and cytokines involved in allergy and inflammation

erythroderma ( J:210758 )

• mild erythroderma is seen at birth, develops into exfoliative erythroderma by 8 days after birth and all mice have mild or severe erythorderma at 1 month of age

abnormal coat appearance ( J:210758 )

• body hair is thinner, lusterless, and spiky with flakes of dry skin on the fur

delayed hair appearance ( J:210758 )

• body hair shows a delay in growth but appears almost normal in nonlesioned adult skin

sparse hair ( J:210758 )

• all mice show sparse fur at 1 month of age

abnormal hair follicle morphology ( J:210758 )

• hair follicles are hyperplastic and disorganized

decreased hair follicle number ( J:210758 )

abnormal vibrissa morphology ( J:210758 )

• vibrissae are disoriented at birth

kinked vibrissae ( J:210758 )

• vibrissae are bent

short vibrissae ( J:210758 )

• vibrissae are short at birth and stay short at 1 year of age

sparse vibrissae ( J:210758 )

• vibrissae are reduced at birth and remain sparse at 1 year of age

abnormal dermis papillary layer morphology ( J:210758 )

• epidermis shows marked papillomatosis before stratum corneum detachment

abnormal epidermal layer morphology ( J:210758 )

• epidermis shows intercellular separation at the granular layer-stratum corneum boundary and detachment of the stratum corneum from the granular layer

• desmosomes are not cohesive at the interface between the granular layer and stratum corneum and these structures are asymmetrically split

• mice, however, show normal epidermal terminal differentiation

hyperkeratosis ( J:210758 )

• epidermis shows marked hyperkeratosis before stratum corneum detachment

parakeratosis ( J:210758 )

• mild parakeratosis in the stratum corneum

• however, no keratohyalin granules are seen in the stratum corneum

acanthosis ( J:210758 )

• epidermis shows marked acanthosis before stratum corneum detachment

abnormal skin appearance ( J:210758 )

• moderate to severe lichenification of the ears

dry skin ( J:210758 )

scaly skin ( J:210758 )

• mice develop scaling of the entire body at 8 days after birth and all mice show scaling at 1 month of age; severity varies between moderate and severe

increased pruritus ( J:210758 )

immune system

enlarged spleen ( J:210758 )

increased activated T cell number ( J:210758 )

• expansion of activated T cells in draining lymph nodes, with a higher proportion of IL4+, IL13+, TNFalpha+ and IL17+ producing T cells compared to wild-type mice

increased IgE level ( J:210758 )

abnormal circulating cytokine level ( J:210758 )

• serum levels of Tslp, a pro-Th2 cytokine, are elevated

enlarged lymph nodes ( J:210758 )

• due to hyperplasia

abnormal inguinal lymph node morphology ( J:210758 )

• increase in the number of cells in inguinal nodes

lymph node inflammation ( J:210758 )

• draining lymph nodes show an increase in number of B cells, monocytes, dendritic cells, and T lymphocytes and a higher proportion of IL4+, IL13+, TNFalpha+ and IL17+ producing T cells compared to wild-type mice

skin inflammation ( J:210758 )

• nonlesional skin shows infiltrates of T cells, mast cells and eosinophil granulocytes in the dermis

• nonlesional skin shows upregulation of chemokines and cytokines involved in allergy and inflammation

erythroderma ( J:210758 )

• mild erythroderma is seen at birth, develops into exfoliative erythroderma by 8 days after birth and all mice have mild or severe erythorderma at 1 month of age

hematopoietic system

enlarged spleen ( J:210758 )

increased activated T cell number ( J:210758 )

• expansion of activated T cells in draining lymph nodes, with a higher proportion of IL4+, IL13+, TNFalpha+ and IL17+ producing T cells compared to wild-type mice

increased IgE level ( J:210758 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Netherton syndrome		DOID:0050474	OMIM:256500	J:210758