Phenotypes associated with this allele

• Allele Symbol: Wasl^tm1.1Ttha
• Allele Name: targeted mutation 1.1, Thirumaran Thanabalu
• Allele ID: MGI:5620949
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Wasl^tm1.1Ttha/Wasl^tm1.1Ttha Tg(KRT14-cre)1Amc/0	involves: C57BL/6 * C57BL/6N * CBA	MGI:6295452
cn2	Wasl^tm1.1Ttha/Wasl^tm1.1Ttha Tg(Nes-cre)1Kag/0	involves: C57BL/6 * SJL	MGI:5662272
cn3	Wasl^tm1.1Ttha/Wasl^+ Tg(Nes-cre)1Kag/0	involves: C57BL/6 * SJL	MGI:5662273

Genotype
MGI:6295452

cn1

• Allelic Composition: Wasl^tm1.1Ttha/Wasl^tm1.1Ttha; Tg(KRT14-cre)1Amc/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * CBA

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

growth/size/body

decreased body weight ( J:271857 )

postnatal growth retardation ( J:271857 )

• stunted growth

mortality/aging

premature death ( J:271857 )

• 10% of mice develop severe atopic dermatitis-like skin and die before 30 days of age

integument

increased keratinocyte proliferation ( J:271857 )

impaired skin barrier function ( J:271857 )

• increase in transepidermal water loss at P15, P23, P30, P60, and P120, with transepidermal water loss 2-fold higher at P15 and 6-8 fold higher at P120

• keratinocytes show reduced expression and localization of tight junction proteins but not adherens junction proteins

skin inflammation ( J:271857 )

• mice develop spontaneous inflammation in the neck and face at 10 weeks after birth, with extensive infiltration of immune cells including mast cells, eosinophils, lymphocytes, monocytes, and neutrophils in skin

dermatitis ( J:271857 )

• 10% of mice develop severe atopic dermatitis-like skin

alopecia ( J:271857 )

epidermal hyperplasia ( J:271857 )

• increase in keratinocyte proliferation resulting in epidermal hyperplasia

• however, hyperproliferation response of epidermis to epidermal stress chemical TPA is similar to controls

thick epidermis ( J:271857 )

abnormal skin appearance ( J:271857 )

• nevi are seen at P180

dry skin ( J:271857 )

scaly skin ( J:271857 )

wrinkled skin ( J:271857 )

cellular

increased keratinocyte proliferation ( J:271857 )

digestive/alimentary system

abnormal esophagus morphology ( J:271857 )

• esophagus exhibits an abnormal mucosa

dilated esophagus ( J:271857 )

• esophagus exhibits a wide lumen size

homeostasis/metabolism

abnormal circulating chemokine level ( J:271857 )

• chemokines such as granulocyte-colony stimulating factor, keratinocyte chemoattractant and eotaxin are increased in the serum

increased circulating interleukin-1 alpha level ( J:271857 )

increased circulating interleukin-17 level ( J:271857 )

increased circulating interleukin-6 level ( J:271857 )

increased circulating tumor necrosis factor level ( J:271857 )

impaired skin barrier function ( J:271857 )

• increase in transepidermal water loss at P15, P23, P30, P60, and P120, with transepidermal water loss 2-fold higher at P15 and 6-8 fold higher at P120

• keratinocytes show reduced expression and localization of tight junction proteins but not adherens junction proteins

immune system

abnormal circulating chemokine level ( J:271857 )

• chemokines such as granulocyte-colony stimulating factor, keratinocyte chemoattractant and eotaxin are increased in the serum

increased circulating interleukin-1 alpha level ( J:271857 )

increased circulating interleukin-17 level ( J:271857 )

increased circulating interleukin-6 level ( J:271857 )

increased circulating tumor necrosis factor level ( J:271857 )

skin inflammation ( J:271857 )

• mice develop spontaneous inflammation in the neck and face at 10 weeks after birth, with extensive infiltration of immune cells including mast cells, eosinophils, lymphocytes, monocytes, and neutrophils in skin

dermatitis ( J:271857 )

• 10% of mice develop severe atopic dermatitis-like skin

increased susceptibility to bacterial infection ( J:271857 )

• mice exhibit increased colonization by S. aureus bacteria, showing an increase in the number of bacterial colonies from skin swab compared to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:271857

Genotype
MGI:5662272

cn2

• Allelic Composition: Wasl^tm1.1Ttha/Wasl^tm1.1Ttha; Tg(Nes-cre)1Kag/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:207484 )

• mice are born phenotypically normal with a near-Mendelian incidence (30% vs. 25% expected); however, all mice die prior to weaning within 3 to 4 weeks after birth (P18-P24)

growth/size/body

decreased body size ( J:207484 )

decreased body weight ( J:207484 )

• at P7, P10 and P13, mice show a significant reduction in average body weight relative to controls

postnatal growth retardation ( J:207484 )

• by P5-P7, mice exhibit noticeably retarded growth rates relative to controls

behavior/neurological

lethargy ( J:207484 )

• at P15, mice exhibit locomotor disturbance with lethargic pace

abnormal gait ( J:207484 )

• at P15, mice exhibit broad-base stance/gait pattern

nervous system

abnormal brain vasculature morphology ( J:207484 )

• at P15, mice show a marked decrease in brain vascularization relative to controls

hydrocephaly ( J:207484 )

• at P15, an unusually large amount of cerebrospinal fluid (CSF) is drained out from the mutant skull during brain isolation

• CSF accumulation in the skull results in brain swelling and enlarged brain hemispheres

obstructive hydrocephaly ( J:207484 )

• hydrocephalus is likely caused by a blocked connection between the third and fourth ventricles

cerebral aqueductal stenosis ( J:207484 )

• the rostral segment of the aqueduct of Sylvius is abnormally narrow or completely collapsed

increased brain size ( J:207484 )

• at P15, mutant brains are noticeably larger than control brains

abnormal brain ependyma morphology ( J:207484 )

• hydrocephalic mice show major defects in the ependymal layer accompanied by a severe denudation of ependymal layers lining the ventricular wall

• N-cadherin immune-staining confirmed defects in ependymal layer integrity

absent brain ependyma motile cilia ( J:207484 )

• at P14-18, immunostaining with anti-acetylated tubulin revealed a severe reduction or absence of ependymal cilia in the lateral ventricles

• SEM micrographs confirmed that the surface of ependymal cells lining the lateral ventricles is relatively smooth and lacks the numerous fine projections seen in controls

enlarged brain ventricles ( J:207484 )

• at 3 weeks of age, hydrocephalic mice show markedly enlarged ventricles in both anterior and posterior regions of lateral ventricles

dilated fourth ventricle ( J:207484 )

• in hydrocephalic mice, dilation of the fourth ventricle is observed

dilated lateral ventricle ( J:207484 )

• at 3 weeks of age, H&E-stained coronal brain sections revealed visibly dilated lateral ventricles along their entire rostrocaudal aspect

abnormal choroid plexus morphology ( J:207484 )

• in hydrocephalic mice, the choroid plexus displays an undefined border with disrupted cell alignment between adjacent cells

abnormal cerebral aqueduct morphology ( J:207484 )

• in hydrocephalic mice, a unique type of columnar cells is absent in the rostral aqueduct wall due to aqueduct atresia and stenosis

• an enlarged lumen is noted in the caudal part of the aqueduct

• abnormal multilayered stratification of the ependymal cells lining along the caudal part of the aqueduct wall and increased cell numbers in the periaqueductal gray regions are observed

decreased corpus callosum size ( J:207484 )

• hydrocephalic mice show a profound reduction in the corpus callosum

abnormal dorsal striatum morphology ( J:207484 )

• hydrocephalic mice show a profound reduction in the caudate putamen

absent hippocampus ( J:207484 )

• strikingly, hydrocephalic mice show absence of hippocampal formation

abnormal cerebral cortex morphology ( J:207484 )

• the spatial alignment and relation of cortical cell orientation are disrupted and compressed by the enlargement of the ventricle system

• however, no significant morphological deterioration is noted in anterior regions of the frontal cortex

thin cerebral cortex ( J:207484 )

• hydrocephalic brains exhibit reduced thickness of the cerebral cortex along its rostral and caudal parts

abnormal septum of telencephalon morphology ( J:207484 )

• hydrocephalic mice show a profound reduction in the cortical layers and septum

abnormal postnatal subventricular zone morphology ( J:207484 )

• Ki-67 staining revealed a significant decrease in cell proliferation in the subventricular zone relative to control mice

astrocytosis ( J:207484 )

• GFAP staining revealed a marked increase in astrocyte density in the cerebral cortex and surrounding areas of the lateral ventricular regions, indicating astrogliosis

• mutant astrocytes tend to have an enlarged cell body and thicker processes than control astrocytes

skeleton

enlarged cranium ( J:207484 )

domed cranium ( J:207484 )

• at ~P10, mice develop a dome shaped skull morphology that becomes more prominent by P15

abnormal spine curvature ( J:207484 )

• at P15, mice display abnormal curvature of the thoracic vertebrae

kyphosis ( J:207484 )

• at P15, mice exhibit a hunchback body posture

craniofacial

enlarged cranium ( J:207484 )

domed cranium ( J:207484 )

• at ~P10, mice develop a dome shaped skull morphology that becomes more prominent by P15

cardiovascular system

abnormal brain vasculature morphology ( J:207484 )

• at P15, mice show a marked decrease in brain vascularization relative to controls

cellular

absent brain ependyma motile cilia ( J:207484 )

• at P14-18, immunostaining with anti-acetylated tubulin revealed a severe reduction or absence of ependymal cilia in the lateral ventricles

• SEM micrographs confirmed that the surface of ependymal cells lining the lateral ventricles is relatively smooth and lacks the numerous fine projections seen in controls

Genotype
MGI:5662273

cn3

• Allelic Composition: Wasl^tm1.1Ttha/Wasl⁺; Tg(Nes-cre)1Kag/0
• Genetic Background: involves: C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:207484 )

• mice have a normal life span and display no obvious defects in external morphology, weight, reproductive vigor, or behavior relative to wild-type controls