Phenotypes associated with this allele

• Allele Symbol: Tfap2b^tm1Rbu
• Allele Name: targeted mutation 1, Reinhard Buettner
• Allele ID: MGI:2180473
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tfap2b^tm1Rbu/Tfap2b^tm1Rbu	129P2.129-Tfap2b^tm1Rbu	MGI:3037833
hm2	Tfap2b^tm1Rbu/Tfap2b^tm1Rbu	involves: 129S1/Sv * 129X1/SvJ	MGI:5292663
hm3	Tfap2b^tm1Rbu/Tfap2b^tm1Rbu	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3037832
ht4	Tfap2b^tm1Rbu/Tfap2b^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5292664
cn5	Tfap2b^tm1Rbu/Tfap2b^tm2Will H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:6152756

Genotype
MGI:3037833

hm1

• Allelic Composition: Tfap2b^tm1Rbu/Tfap2b^tm1Rbu
• Genetic Background: 129P2.129-Tfap2b^tm1Rbu

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

mortality/aging

postnatal lethality, complete penetrance ( J:83000 )

• animals die between 10 and 14 days of birth

behavior/neurological

tremors ( J:83000 )

• described as shivering and trembling behavior

growth/size/body

kidney cyst ( J:83000 )

• tubular or collecting duct cysts present with variable penetrance

postnatal growth retardation ( J:83000 )

• animals are significantly smaller by postnatal day 4

homeostasis/metabolism

increased circulating creatinine level ( J:83000 )

increased blood urea nitrogen level ( J:83000 )

increased circulating parathyroid hormone level ( J:83000 )

abnormal ion homeostasis ( J:83000 )

decreased circulating calcium level ( J:83000 )

• reduced calcium level in the serum

increased circulating phosphate level ( J:83000 )

decreased urine calcium level ( J:83000 )

decreased urine osmolality ( J:83000 )

limbs/digits/tail

polydactyly ( J:83000 )

• additional sixth digit, postaxial hexadactyly

muscle

muscle spasm ( J:83000 )

• described as tetanic cramps

renal/urinary system

kidney cyst ( J:83000 )

• tubular or collecting duct cysts present with variable penetrance

decreased urine calcium level ( J:83000 )

decreased urine osmolality ( J:83000 )

dilated proximal convoluted tubule ( J:83000 )

• dilated tubules present with variable penetrance

abnormal kidney physiology ( J:83000 )

• tubular function defects, but normal glomerular function

integument

scaly skin ( J:83000 )

• described as dry and scaly

Genotype
MGI:5292663

hm2

• Allelic Composition: Tfap2b^tm1Rbu/Tfap2b^tm1Rbu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

Postaxial accessory digits in Tfap2b^tm1Rbu/Tfap2b^tm1Rbu mice

mortality/aging

neonatal lethality, incomplete penetrance ( J:175832 )

• most pups die within 24 h of birth

cardiovascular system

pulmonary vascular congestion ( J:175832 )

• progressive capillary congestion in newborns

patent ductus arteriosus ( J:175832 )

• in all mice at 2 h and 6 h post birth

congestive heart failure ( J:175832 )

limbs/digits/tail

postaxial polydactyly ( J:175832 )

• an additional finger-like structure (with a single phalange and no nail) grows out laterally from the 5th finger on the forelimbs of all mice

• extra digits are seen on hindlimbs in only 5% of mice

respiratory system

pulmonary vascular congestion ( J:175832 )

• progressive capillary congestion in newborns

abnormal pulmonary alveolar system morphology ( J:175832 )

• disorganized and shrunken alveolar structure that is more severely affected in dying and dead pups

cellular

patent ductus arteriosus ( J:175832 )

• in all mice at 2 h and 6 h post birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Char syndrome		DOID:0060563	OMIM:169100	J:175832

Genotype
MGI:3037832

hm3

• Allelic Composition: Tfap2b^tm1Rbu/Tfap2b^tm1Rbu
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:42260 )

• more than half of the homozygous neonates died after birth; the remainder died within the first postnatal day

renal/urinary system

increased kidney apoptosis ( J:42260 )

• widespread apoptosis of collecting duct and distal tubular epithelia was noted at birth

increased renal tubule apoptosis ( J:42260 )

• widespread apoptosis of distal tubular epithelia was noted at birth

kidney cyst ( J:42260 )

• kidney cysts seen in the collecting duct system and distal tubuli; cysts are first detectable at E18.5 but do not fully develop until after birth

small kidney ( J:42260 )

cellular

increased kidney apoptosis ( J:42260 )

• widespread apoptosis of collecting duct and distal tubular epithelia was noted at birth

increased renal tubule apoptosis ( J:42260 )

• widespread apoptosis of distal tubular epithelia was noted at birth

growth/size/body

kidney cyst ( J:42260 )

• kidney cysts seen in the collecting duct system and distal tubuli; cysts are first detectable at E18.5 but do not fully develop until after birth

Genotype
MGI:5292664

ht4

• Allelic Composition: Tfap2b^tm1Rbu/Tfap2b⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cardiovascular system

patent ductus arteriosus ( J:175832 )

• in 1 of 8 mice at 2 h post birth

limbs/digits/tail

postaxial polydactyly ( J:175832 )

• an additional finger-like structure (with a single phalange and no nail) grows out laterally from the 5th finger on the forelimbs of 18.2% of mice

cellular

patent ductus arteriosus ( J:175832 )

• in 1 of 8 mice at 2 h post birth

Genotype
MGI:6152756

cn5

• Allelic Composition: Tfap2b^tm1Rbu/Tfap2b^tm2Will; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

vision/eye

abnormal eye morphology ( J:234170 )

• presence of a severe and fully penetrant closed angle phenotype that develops prior to 2 months of age indicating glaucomatous pathology

decreased amacrine cell number ( J:234170 )

• mice exhibit fewer displaced amacrine cells in the ganglion cell layer at 2 months of age

retina ganglion cell degeneration ( J:234170 )

• loss of retinal ganglion cells and their axons in 2 month old retina, with loss of axons occurring in a segmental, fan-shaped manner

abnormal optic disk morphology ( J:234170 )

• damage of the optic nerve head

optic nerve cupping ( J:234170 )

• retinal ganglion cell axon loss is associated with damage of the optic nerve head, indicative of excavation or cupping

optic nerve degeneration ( J:234170 )

• optic nerves exhibit decreased number of myelinated axons, the presence of degenerating axons and areas of severe atrophy in 2 month old mice

optic nerve atrophy ( J:234170 )

• areas of severe optic nerve atrophy is seen in 2 month old mice

abnormal iridocorneal angle ( J:234170 )

• the iridocorneal angle is disrupted with the iris adherent to the cornea, creating a closed angle phenotype

• defects in the angle tissue are present at E18.5

abnormal ciliary body morphology ( J:234170 )

• the ciliary body is malformed in 2-3 month old mice and is potentially rudimentary as it lacks its normally convoluted and lobulated structure

abnormal cornea morphology ( J:234170 )

• at E15.5, the cornea is less compact, with large gaps within the stroma

• multiple defects of the corneal layers derived from the periocular mesenchyme are seen in 2-3 month old mice, including the lack of a clear endothelial layer and a less cohesive corneal stroma

• corneolenticular adhesion

cornea vascularization ( J:234170 )

• presence of red blood cells in the corneal stroma at E18.5

• marker analysis indicates the presence of blood vessels in the cornea of 2 month old mice, indicating vascularization of the cornea

anterior iris synechia ( J:234170 )

• the iris is adherent to the cornea

• adhesion between the cornea and iris detected 360 degrees around the eye

absent cornea endothelium ( J:234170 )

• lack of a clear endothelial layer in the cornea of 2-3 month old mice

• defects in the corneal endothelium are present at E18.5

abnormal cornea epithelium morphology ( J:234170 )

• 2-3 month old mice exhibit reduced stratification of the corneal epithelial layer

decreased cornea epithelium thickness ( J:234170 )

• the corneal epithelial layer is reduced in thickness

abnormal cornea stroma morphology ( J:234170 )

• large gaps within the stroma are seen at E15.5

• the corneal stroma is less cohesive in 2-3 month old mice

fused cornea and lens ( J:234170 )

• cornea and lens adhere to one another at E15.5

abnormal eye anterior chamber morphology ( J:234170 )

• multiple malformations of the anterior chamber are seen in 2-3 month old mice

abnormal lens epithelium morphology ( J:234170 )

• lens epithelium is disorganized and multi-layered in 2-3 month old mice, characteristic of a cataract

anterior subcapsular cataract ( J:234170 )

thin retina inner plexiform layer ( J:234170 )

decreased total retina thickness ( J:234170 )

• retinal thickness is decreased in 2-3 month old mice, mainly due to thinning of the inner plexiform layer

eye opacity ( J:234170 )

• ocular opacity is seen after eyelid opening that persists as mice age

ocular hypertension ( J:234170 )

• approximate 3-fold elevation of intraocular pressure is seen in 3 month old mice

cardiovascular system

cornea vascularization ( J:234170 )

• presence of red blood cells in the corneal stroma at E18.5

• marker analysis indicates the presence of blood vessels in the cornea of 2 month old mice, indicating vascularization of the cornea

nervous system

gliosis ( J:234170 )

• expression of GFAP is upregulated in Muller glia, indicating gliosis

decreased amacrine cell number ( J:234170 )

• mice exhibit fewer displaced amacrine cells in the ganglion cell layer at 2 months of age

retina ganglion cell degeneration ( J:234170 )

• loss of retinal ganglion cells and their axons in 2 month old retina, with loss of axons occurring in a segmental, fan-shaped manner

abnormal optic disk morphology ( J:234170 )

• damage of the optic nerve head

optic nerve cupping ( J:234170 )

• retinal ganglion cell axon loss is associated with damage of the optic nerve head, indicative of excavation or cupping

optic nerve degeneration ( J:234170 )

• optic nerves exhibit decreased number of myelinated axons, the presence of degenerating axons and areas of severe atrophy in 2 month old mice

optic nerve atrophy ( J:234170 )

• areas of severe optic nerve atrophy is seen in 2 month old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
angle-closure glaucoma		DOID:13550		J:234170