Foxe3<dyl> Spontaneous Allele Detail MGI Mouse (MGI:1856851)

Foxe3^dyl
Spontaneous Allele Detail

Nomenclature

Symbol:	Foxe3^dyl
Name:	forkhead box E3; dysgenetic lens
MGI ID:	MGI:1856851
Synonyms:	dyl
Gene:	Foxe3 Location: Chr4:114597752-114598618 bp, - strand Genetic Position: Chr4, 49.6 cM, cytoband C7

Mutation
origin

Strain of Origin:

BALB/cLiA

Mutation
description

Allele Type:	Spontaneous
Mutation:	Single point mutation
	Two missense mutations in the sequences encoding the forkhead domain were shown to cosegregate with the dyl phenotype: two C to T transitions at positions 277 and 293 that change codons 93 and 98 from phenylalanine to leucine and serine respectively. These mutations are in a region of the protein thought to be critical for DNA binding. (J:59880)
Inheritance:	Recessive

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Foxe3 Mutation:	1 strain or line available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	ht2	ht3
behavior/neurological		√
abnormal pupillary reflex		√
		hm1	ht2	ht3
cardiovascular system		√
corneal vascularization		√
		hm1	ht2	ht3
vision/eye		√	√	√
abnormal pupillary reflex		√
microphthalmia		√
abnormal anterior eye segment morphology			√
abnormal iridocorneal angle		√
abnormal canal of Schlemm morphology		√
absent trabecular meshwork		√
abnormal ciliary body morphology		√
abnormal iris morphology		√	√
small pupils		√
iris hypoplasia			√
corneal adhesion to iris			√
abnormal cornea morphology		√
corneal vascularization		√
abnormal corneal endothelium morphology		√	√
abnormal corneal epithelium morphology		√
abnormal corneal stroma morphology		√	√
corneal opacity		√
fused cornea and lens		√		√
abnormal lens morphology		√
abnormal lens development		√		√
abnormal lens vesicle development		√
abnormal lens epithelium morphology		√
abnormal lens fiber morphology		√
cataracts		√		√
small lens		√		√

		hm1	ht2	ht3
Disease Models		√
Anterior Segment Mesenchymal Dysgenesis; ASMD		√
Peters Anomaly		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

hm1 Disease Model

Foxe3^dyl/Foxe3^dyl

BALB/cLiA-Foxe3^dyl

vision/eyeabnormal pupillary reflex (J:6131)

pupillary reaction is absent

abnormal iridocorneal angle (J:119940)

filtration angle is severely malformed and ruptures in the tissue frequently occur, while in most sections, it is missing

abnormal canal of Schlemm morphology (J:119940)

absent trabecular meshwork (J:119940)

filtration angle is without a trabecular meshwork

abnormal ciliary body morphology (J:119940)

iris and ciliary body are replaced by single structure resembling a stunted iris

zonular fibers reach up between posterior surface and lens

histologically, the structure present does not resemble iris or ciliary body, with stromal and epithelial parts are compact, and structure lacks secretory apparatus, fenestrated capillaries, and musculature of the normal ciliary body

abnormal iris morphology (J:6131, J:119940)

iris shows adhesive attachment with the lens (J:6131)

iris and ciliary body are replaced by single structure resembling a stunted iris (J:119940)

anterior surface of structure is made up of stromal cells; histologically it does not resemble iris or ciliary body, with stromal and epithelial parts are compact and homogeneous lacking muscle cells, blood vessels, nerves and channels in extracellular space like a normal iris (J:119940)

small pupils (J:6131)

abnormal cornea morphology (J:6131, J:76605, J:7448, J:119940)

about 40% exhibit uni- or bilateral corneal irregularities that include depressions or blisters in the cornea (J:76605)

exhibit a persistent central stalk-like connection between the lens and cornea; stalk consists of epithelial cells continuous with the subcapsular lens epithelium (J:76605)

the persistent stalk connection distorts the curvature of the cornea and the anterior face of the lens (J:76605)

the cornea is not well defined at E13 (J:7448)

stratification of cornea is less pronounced than in wild-type (J:119940)

corneal vascularization (J:6131)

seen in older mutants

abnormal corneal endothelium morphology (J:119940)

endothelium does not develop normally

inner corneal surface is covered by crowded and disorganized layer of cells resembling stromal cells of fused iris/ciliary body

there is a high melanosome content in corneal endothelium; these often adhere to the 'iris/ciliary body stroma'

mutants show high levels of N-cadherin in all mesenchyme facing the anterior chamber, while in wild-type it is seen in iris epithelium in minute amounts

abnormal corneal epithelium morphology (J:6131)

the corneal epithelium is interrupted in the region where the persistent connection between the lens and the corneal epithelium occurs

abnormal corneal stroma morphology (J:76605, J:119940)

corneal swelling associated with a lax, cavernous structure of the stroma is a source of leucoma (J:76605)

mild dysplasia of the corneal stroma (J:76605)

stroma shows a reduction in number and density of collagen fibers (J:119940)

corneal opacity (J:6131, J:76605)

varying degrees of corneal opacity, ranging from a few tiny spots in the papillary area to a completely opaque central cornea (J:6131)

minor central leucoma (J:76605)

fused cornea and lens (J:76605, J:59880, J:119940)

in some mutants, the anterior surface of the lens and the posterior surface of the cornea adhere directly to each other without a connecting stalk (J:76605)

lens vesicle fails to separate from the ectoderm, causing a fusion between the lens and cornea (J:59880)

mice show fusion between cornea and small cataractic lens resulting from failure of lens vesicle to close and separate from surface ectoderm (J:119940)

in adults, connection may be broken, leaving on central part of external corneal surface a deposit of tissue derived from interior of lens vesicle (J:119940)

abnormal lens morphology (J:6131, J:7448)

lens is irregularly shaped (J:6131)

exhibit a persistent connection between the lens and the corneal epithelium (J:6131)

at E16, part of the lens protrudes to the exterior and eventually materials from the lens interior are expelled (J:6131)

extrusion of lens crystalline materials through the stalk, resulting in a reduced and malformed lens (J:7448)

abnormal lens development (J:76605, J:7448)

exhibit a persistent central stalk-like connection between the lens and cornea (J:76605)

the lens fails to separate from the cranial ectoderm at E12 (J:7448)

abnormal lens vesicle development (J:6131, J:59880, J:7448, J:119940)

the lens vesicle fails to separate from the ectoderm at E10 (J:6131)

the lens vesicle fails to close which in some cases leads to lens material being ejected to the exterior (J:59880)

at E11, the margin of the lens vesicle pit remains open (J:7448)

reduction in lens vesicle tissue volume is similar to that observed in Foxe3^dyl homozygotes, while in Foxe3-heterozygotes volume reduction is intermediate between homozygotes and wild-type (J:119940)

abnormal lens epithelium morphology (J:59880)

the lens epithelial layer forms during lens vesicle polarization but then gradually disappears and is absent by the time of birth

the posterior cells of the epithelium fail to divide and show signs of premature differentiation and the most anterior cells are eliminated by apoptosis

abnormal lens fiber morphology (J:6131, J:59880, J:7448)

some fibrous structures are found in the lens but they are very disorganized and interspersed by large irregular vacuoles (J:6131)

the lens epithelium fails to proliferate leading to a reduction in the number of secondary lens fibers (J:59880)

in the E13 lens, the cortical fibers appear less elongated and less regularly aligned (J:7448)

appearance of vacuoles in the lens nucleus and cortex marks the beginning of degeneration of fibers (J:7448)

cataracts (J:59880, J:6131, J:76605, J:7448)

lens appears cataractous at E16 (J:6131)

clusters of disorganized cells underneath the lens capsule may cause local cataracts (J:76605)

in the E16 lens, vacuoles appear all over the cortex and nucleus as a result of cataractous degeneration (J:7448)

small lens (J:59880, J:7448, J:6131)

smaller lenses are seen by E13 (J:6131)

microphthalmia (J:6131)

small size of the eye varies between individuals and also sometimes between the two eyes of the same individual

behavior/neurologicalabnormal pupillary reflex (J:6131)

pupillary reaction is absent

cardiovascular systemcorneal vascularization (J:6131)

seen in older mutants

Mouse Models of Human Disease	Note	Ref(s)
Models with phenotypic similarity to human diseases associated with human FOXE3.
Anterior Segment Mesenchymal Dysgenesis; ASMD		J:59880
Models with phenotypic similarity to human diseases not associated with human FOXE3.
Peters Anomaly		J:59880, J:6131, J:76605

ht2

Foxe3^dyl/Foxe3⁺

BALB/cLiA-Foxe3^dyl

ht3

Foxe3^dyl/Foxe3^tm1Pca

C.Cg-Foxe3^dyl/Foxe3^tm1Pca

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models with phenotypic similarity to human diseases associated with human FOXE3.
Anterior Segment Mesenchymal Dysgenesis; ASMD OMIM ID: 107250		hm1	Foxe3^dyl/Foxe3^dyl	BALB/cLiA-Foxe3^dyl	J:59880
Models with phenotypic similarity to human diseases not associated with human FOXE3.
Peters Anomaly OMIM ID: 604229		hm1	Foxe3^dyl/Foxe3^dyl	BALB/cLiA-Foxe3^dyl	J:59880, J:6131, J:76605

References

Original:	J:6131 Sanyal S et al., "Dysgenetic lens (dyl)--a new gene in the mouse." Invest Ophthalmol Vis Sci 1979 Jun;18(6):642-5
All:	8 reference(s)

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