Phenotypes associated with this allele

• Allele Symbol: Spink5^tm1Drh
• Allele Name: targeted mutation 1, Duncan R Hewett
• Allele ID: MGI:3527214
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spink5^tm1Drh/Spink5^tm1Drh	involves: 129P2/OlaHsd * C57BL/6	MGI:3527451
cx2	Klk6^tm1Gsot/Klk6^tm1Gsot Spink5^tm1Drh/Spink5^tm1Drh	involves: 129P2/OlaHsd * C57BL/6	MGI:6444340

Genotype
MGI:3527451

hm1

• Allelic Composition: Spink5^tm1Drh/Spink5^tm1Drh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:95549 )

• homozygotes develop a dry and wrinkled appearance and die with 1-2 hours after birth from severe dehydration

homeostasis/metabolism

dehydration ( J:95549 )

• rapid dehydration despite normal feeding behavior is seen after birth

impaired skin barrier function ( J:95549 )

• skin barrier function is normal before birth but breaks down after birth in correlation with skin shedding resulting in increased transepidermal water loss

integument

impaired skin barrier function ( J:95549 )

• skin barrier function is normal before birth but breaks down after birth in correlation with skin shedding resulting in increased transepidermal water loss

abnormal epidermal layer morphology ( J:95549 )

• adhesion is lost in the transitional layer between the stratum corneum and granular layer

abnormal corneocyte envelope morphology ( J:95549 )

• the cornified envelope is more fragile in mutants than in wild-type mice

hyperkeratosis ( J:95549 )

• mild hyperkeratosis is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Netherton syndrome		DOID:0050474	OMIM:256500	J:95549

Genotype
MGI:6444340

cx2

• Allelic Composition: Klk6^tm1Gsot/Klk6^tm1Gsot; Spink5^tm1Drh/Spink5^tm1Drh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:289877 )

• mice survive up to 5 hours after birth and die from severe epidermal barrier defect

integument

integument phenotype ( J:289877 )

N • mice exhibit normal epidermal differentiation

impaired skin barrier function ( J:289877 )

• severe epidermal barrier defect, with mice losing water with the same rate at single Spink5^tm1Drh homozygotes

abnormal vibrissa morphology ( J:289877 )

• vibrissae defects

abnormal skin morphology ( J:289877 )

• mice display a similar skin phenotype as single Spink5^tm1Drh homozygotes

abnormal epidermis stratum corneum morphology ( J:289877 )

• stratum corneum detachment

epidermal desquamation ( J:289877 )

• severe desquamation

immune system

abnormal cytokine level ( J:289877 )

• mice show reduced levels of inflammatory cytokine expression compared to single Spink5^tm1Drh homozygotes, including Tslp, Tnf-alpha, Il-16, Il-6, Il-17a, Il-13, and Il-4

decreased inflammatory response ( J:289877 )

• mice exhibit reduced epidermal inflammation seen in single Spink5^tm1Drh homozygotes, showing reduced mast cell infiltration in the epidermis and reduced levels of inflammatory cytokine expression

homeostasis/metabolism

impaired skin barrier function ( J:289877 )

• severe epidermal barrier defect, with mice losing water with the same rate at single Spink5^tm1Drh homozygotes

abnormal cytokine level ( J:289877 )

• mice show reduced levels of inflammatory cytokine expression compared to single Spink5^tm1Drh homozygotes, including Tslp, Tnf-alpha, Il-16, Il-6, Il-17a, Il-13, and Il-4