Phenotypes associated with this allele

• Allele Symbol: Trp63^tm3Aam
• Allele Name: targeted mutation 3, Alea A Mills
• Allele ID: MGI:6477377
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Trp63^tm3Aam/Trp63^tm3Aam	involves: 129S7/SvEvBrd	MGI:6477394
ht2	Trp63^tm3Aam/Trp63^+	involves: 129S7/SvEvBrd	MGI:6477390
ht3	Trp63^tm2.1Aam/Trp63^tm3Aam	involves: 129S7/SvEvBrd	MGI:6477405

Genotype
MGI:6477394

hm1

• Allelic Composition: Trp63^tm3Aam/Trp63^tm3Aam
• Genetic Background: involves: 129S7/SvEvBrd

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

mortality/aging

perinatal lethality, complete penetrance ( J:294158 )

embryo

abnormal embryo development ( J:294158 )

• defects in epithelial morphogenesis

integument

abnormal skin development ( J:294158 )

• neonates lack a mature skin barrier

limbs/digits/tail

abnormal limb morphology ( J:294158 )

• neonates exhibit severe limb defects including limb truncations

short limbs ( J:294158 )

• limb truncations

Genotype
MGI:6477390

ht2

• Allelic Composition: Trp63^tm3Aam/Trp63⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

perinatal lethality, incomplete penetrance ( J:294158 )

• fewer than the expected numbers of mice are seen at weaning with 18% lethality; lethality is apparent at birth

growth/size/body

abnormal tooth development ( J:294158 )

• defective tooth morphogenesis with abnormal root structures and hyperdontia

supernumerary teeth ( J:294158 )

abnormal tooth root morphology ( J:294158 )

• abnormal root structures

abnormal palatal shelf fusion at midline ( J:294158 )

• palatal shelves have not fused at E18.5

• adhesion and fusion of the secondary palate is stalled in a subset of E15 fetuses, appearing similar to palates of E13.5 wild-type mice

cleft palate ( J:294158 )

• severe cleft palate, with 15.4% of neonates exhibiting clefting

behavior/neurological

absent gastric milk in neonates ( J:294158 )

• newborns with cleft palate show absence of a milk pouch in the stomach

craniofacial

abnormal tooth development ( J:294158 )

• defective tooth morphogenesis with abnormal root structures and hyperdontia

supernumerary teeth ( J:294158 )

abnormal tooth root morphology ( J:294158 )

• abnormal root structures

abnormal palatal shelf fusion at midline ( J:294158 )

• palatal shelves have not fused at E18.5

• adhesion and fusion of the secondary palate is stalled in a subset of E15 fetuses, appearing similar to palates of E13.5 wild-type mice

cleft palate ( J:294158 )

• severe cleft palate, with 15.4% of neonates exhibiting clefting

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:294158 )

• palatal shelves have not fused at E18.5

• adhesion and fusion of the secondary palate is stalled in a subset of E15 fetuses, appearing similar to palates of E13.5 wild-type mice

cleft palate ( J:294158 )

• severe cleft palate, with 15.4% of neonates exhibiting clefting

integument

alopecia ( J:294158 )

• mice exhibit alopecia with age

ruffled hair ( J:294158 )

• mice exhibit ruffled coat with age

nail dystrophy ( J:294158 )

• dystrophic nails

abnormal keratinocyte physiology ( J:294158 )

• primary keratinocytes exhibit reduced proliferation and a corresponding increase in cellular senescence

• however, no major skin abnormalities are seen at E16.5 or P0

decreased keratinocyte proliferation ( J:294158 )

• primary keratinocytes exhibit reduced proliferation

limbs/digits/tail

abnormal limb morphology ( J:294158 )

• anomalies of the distal limbs

skeleton

abnormal tooth development ( J:294158 )

• defective tooth morphogenesis with abnormal root structures and hyperdontia

supernumerary teeth ( J:294158 )

abnormal tooth root morphology ( J:294158 )

• abnormal root structures

vision/eye

abnormal eye morphology ( J:294158 )

• mice exhibit eye squinting with age

cellular

decreased keratinocyte proliferation ( J:294158 )

• primary keratinocytes exhibit reduced proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3		DOID:0060783	OMIM:604292	J:294158

Genotype
MGI:6477405

ht3

• Allelic Composition: Trp63^tm2.1Aam/Trp63^tm3Aam
• Genetic Background: involves: 129S7/SvEvBrd

craniofacial

cleft palate ( J:294158 )

• 95% of neonates exhibit cleft palate

digestive/alimentary system

cleft palate ( J:294158 )

• 95% of neonates exhibit cleft palate

growth/size/body

cleft palate ( J:294158 )

• 95% of neonates exhibit cleft palate

integument

thick dermal layer ( J:294158 )

• dermis is thicker in large areas of the skin

abnormal epidermal layer morphology ( J:294158 )

• epidermis is abnormal with the stratum basale and stratum spinosum affected; thickening of Trp63-, K14-, and K10-expressing layers in patches of the epidermis covering the skin surface

thick epidermis stratum basale ( J:294158 )

thick epidermis stratum spinosum ( J:294158 )

limbs/digits/tail

abnormal limb morphology ( J:294158 )

• 100% of neonates exhibit limb defects, ranging from lack of hindlimbs to single ectrodactyly

ectrodactyly ( J:294158 )

• single ectrodactyly in some neonates