Phenotypes associated with this allele

• Allele Symbol: Foxc1^tm1Blh
• Allele Name: targeted mutation 1, Brigid L Hogan
• Allele ID: MGI:1857869
• Summary: 17 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxc1^tm1Blh/Foxc1^tm1Blh	involves: 129S6/SvEvTac	MGI:3811362
hm2	Foxc1^tm1Blh/Foxc1^tm1Blh	involves: 129S6/SvEvTac * Black Swiss	MGI:2177671
ht3	Foxc1^tm1Blh/Foxc1^+	129S6/SvEvTac-Foxc1^tm1Blh	MGI:3811484
ht4	Foxc1^tm1Blh/Foxc1^+	B6.Cg-Foxc1^tm1Blh	MGI:3655827
ht5	Foxc1^tm1Blh/Foxc1^+	involves: 129S6/SvEvTac * Black Swiss	MGI:3811488
ht6	Foxc1^tm1Blh/Foxc1^+	involves: 129S6/SvEvTac * C57BL/6J	MGI:3811486
ht7	Foxc1^tm1Blh/Foxc1^+	involves: 129S6/SvEvTac * CAST/Ei	MGI:3811485
ht8	Foxc1^hith/Foxc1^tm1Blh	involves: 129S6/SvEvTac * C57BL/6J	MGI:4437878
cn9	Foxc1^tm1Tsku/Foxc1^tm1Blh Tg(Tek-cre)1Rwng/0	involves: 129S6/SvEvTac * FVB/N	MGI:3798681
cx10	Foxc1^tm1Blh/Foxc1^+ Tyr^c-2J/Tyr^c-2J	B6.Cg-Tyr^c-2J Foxc1^tm1Blh	MGI:3655825
cx11	Foxc1^tm1Blh/Foxc1^tm1Blh Foxc2^tm1Blh/Foxc2^+	involves: 129S6/SvEvTac	MGI:3811363
cx12	Foxc1^tm1Blh/Foxc1^tm1Blh Foxc2^tm1Blh/Foxc2^tm1Blh	involves: 129S6/SvEvTac	MGI:3811359
cx13	Foxc1^tm1Blh/Foxc1^+ Foxc2^tm1Blh/Foxc2^tm1Blh	involves: 129S6/SvEvTac	MGI:3811361
cx14	Foxc1^tm1Blh/Foxc1^tm1Blh Foxc2^tm1Blh/Foxc2^tm1Blh	involves: 129S6/SvEvTac * Black Swiss	MGI:2170676
cx15	Foxc1^tm1Blh/Foxc1^+ Foxc2^tm1Blh/Foxc2^+	involves: 129S6/SvEvTac * Black Swiss	MGI:2170671
cx16	Foxc1^tm1Blh/Foxc1^tm1Blh Foxc2^tm1Blh/Foxc2^+	involves: 129S6/SvEvTac * Black Swiss	MGI:3622548
cx17	Foxc1^tm1Blh/Foxc1^+ Foxc2^tm1Blh/Foxc2^tm1Blh	involves: 129S6/SvEvTac * Black Swiss	MGI:3622549

Genotype
MGI:3811362

hm1

• Allelic Composition: Foxc1^tm1Blh/Foxc1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac

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

nervous system

abnormal neuron differentiation ( J:157301 )

• at E14.5, the number of intermediate progenitor cells is decreased compared to in wild-type mice

abnormal neuron proliferation ( J:157301 )

• at E14.5, neuron proliferation in the cortex is reduced compared to in wild-type mice

abnormal forebrain morphology ( J:157301 )

• at E12.5, dorsal forebrain lengthening is observed unlike in wild-type mice

• at E14.5, the dorsal forebrain is longer and thinner than in wild-type mice

• however, treatment with all-trans retinoic acid restores forebrain morphology

abnormal cerebral cortex morphology ( J:157301 )

• at E18.5

abnormal stratification in cerebral cortex ( J:157301 )

• at E18.5, cortical layers are disorganized compared to in wild-type mice

abnormal brain meninges morphology ( J:157301 )

• at E14.5, meningeal cells end before the ventral forebrain with absent dorsal meninges unlike in wild-type mice

embryo

embryo phenotype ( J:91443 )

N • somites develop normally

cellular

abnormal neuron differentiation ( J:157301 )

• at E14.5, the number of intermediate progenitor cells is decreased compared to in wild-type mice

abnormal neuron proliferation ( J:157301 )

• at E14.5, neuron proliferation in the cortex is reduced compared to in wild-type mice

Genotype
MGI:2177671

hm2

• Allelic Composition: Foxc1^tm1Blh/Foxc1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

neonatal lethality, complete penetrance ( J:48079 , J:57677 , J:105944 )

• mutants die soon after birth due to an inability to breathe (J:57677)

• mice die at birth (J:105944)

reproductive system

ovary hemorrhage ( J:105944 )

♀ • large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host

decreased oocyte number ( J:105944 )

♀ • ovaries contain fewer germ cells that are found in clusters scattered throughout the ovary unlike in wild-type mice

oocyte degeneration ( J:105944 )

♀ • after 8 weeks of engraftment into a wild-type host, ovaries display oocyte degeneration or loss

abnormal primordial germ cell migration ( J:105944 )

• between E10.5 and E11.5, fewer than normal primordial germ cells migrate out of the hindgut resulting in fewer germ cells entering the developing gonads

• however, germ cell attractants are normally expressed

abnormal ovary morphology ( J:105944 )

♀ • ovaries lack distinct cortex and medulla regions as in wild-type ovaries

♀ • granulosa and thecal cell layers as well as the basement membrane separating the two are less well defined than in wild-type mice

♀ • after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice

♀ • by week 8 after engraftment into a wild-type host, 1 of 4 ovaries contain Seroli cells tubule-like structures

abnormal ovarian cortex morphology ( J:105944 )

♀ • at E18.5, mutant ovaries lack a distinct cortex region

abnormal ovarian follicle morphology ( J:105944 )

♀ • by 8 weeks of engraftment into a wild-type host, remaining healthy follicles are larger than in wild-type mice

impaired ovarian folliculogenesis ( J:105944 )

♀ • when ovaries are transplanted into a wild-type host, follicles fail to progress beyond the pre-antral/early antral stages

polyovular ovarian follicle ( J:105944 )

♀ • after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice

abnormal ovarian medulla morphology ( J:105944 )

♀ • at E18.5, mutant ovaries lack a distinct medulla region

small ovary ( J:105944 )

♀ • at E18.5, mutant ovaries are smaller than wild-type

ovary cyst ( J:105944 )

♀ • large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host

disorganized testis cords ( J:105944 )

♂ • seminiferous cords are present but interspersed with regions of disorganized cells where no cords are apparent

abnormal testis tunica albuginea morphology ( J:105944 )

♂ • at E18.5, testes exhibit a reduced tunica albuginea

abnormal oviduct morphology ( J:105944 )

♀ • the oviduct is shorter than normal and uncoiled

short oviduct ( J:105944 )

♀

small gonad ( J:105944 )

• by E14.5, gonads are reduced compared to in wild-type mice

• mice exhibit smaller and misshapen gonads, especially in the posterior regions, compared to in wild-type mice

small testis ( J:105944 )

♂

embryo

abnormal pharyngeal arch artery morphology ( J:57677 )

• major malformations in the branchial arch arteries and heart are found in all double heterozygotes

abnormal fourth pharyngeal arch artery morphology ( J:57677 )

• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4

abnormal mesonephros morphology ( J:105944 )

• mice exhibit a reduction in the posterior mesonephros with abnormal indentation

• at E14.5, the mesonephric tissues remain enlarged compared to in wild-type mice

• ectopic mesonephric tubules persist up to E18.5

skeleton

abnormal skeleton morphology ( J:48079 )

• newborns have extinsive abnormalities in the skull, vertebrae, thorax, hyoid, larynx, and appendicular skeleton

abnormal craniofacial bone morphology ( J:48079 )

small basisphenoid bone ( J:48079 )

• in newborns the basisphenoid bone is reduced and malformed

absent neurocranium ( J:48079 )

• in newborns the calvarial bones are absent

abnormal maxillary zygomatic process morphology ( J:48079 )

• the zygomatic process is enlarged and fused to the mandible

enlarged maxillary zygomatic process ( J:48079 )

abnormal tarsal bone morphology ( J:48079 )

• in newborns the digits are thinner than normal with smaller ossification centers

abnormal humerus morphology ( J:48079 )

abnormal deltoid tuberosity morphology ( J:48079 )

• in newborns the deltoid process of the humerus is misshapen

abnormal xiphoid process morphology ( J:48079 )

• in newborns the xiphoid process is misshapen

absent sternum ( J:57677 )

• the absence of the sternum presumably contributes to the inability of these mutants to breath

thin ribs ( J:48079 )

• in newborns the ribs are thinner than normal

abnormal vertebral arch morphology ( J:48079 )

• in newborns the dorsal neural arches fail to fuse along the whole vetebral column

• in newborns the lateral arches are reduced

• at E16.5 and birth the neural arches are misshapen and have reduced ossification

small vertebral body ( J:48079 )

• in newborns the vetebral bodies are reduced

abnormal bone ossification ( J:48079 )

• ossification of some of bones is impaired

abnormal sternum ossification ( J:48079 )

• in newborns all of the ossification centers of the sternum except the manubrium are absent

• at E13.5 the mesenchyme cells condense much less than in wild-type

vision/eye

abnormal lacrimal gland morphology ( J:107208 )

• at E18.5, lactimal ducts are distended; the overall length of the gland duct is significantly reduced

abnormal exorbital lacrimal gland morphology ( J:107208 )

• at E18.5, the exorbital lobe is severely reduced compared to in wild-type mice

• significantly fewer branches and terminal buds are observed within the exorbital lobe

absent intraorbital lacrimal gland ( J:107208 )

• at E18.5, the intra-orbital lacrimal gland is absent

abnormal lacrimal gland branching morphogenesis ( J:107208 )

• at E16.5, branches of the lacrimal gland are shorter and wider with fewer terminal buds than in wild-type mice

• lacrimal gland explants have fewer branches with terminal buds that are longer and wider than in wild-type lacrimal explants

• however, lacrimal gland epithelium differentiation is normal

abnormal lacrimal gland physiology ( J:107208 )

• lacrimal gland mesenchyme is insensitive to Bmp7 treatment unlike wild-type mesenchyme

• however, lacrimal gland epithelium proliferation in response to FGF is normal

iris hypoplasia ( J:48079 )

• reduced number of mesenchymal cells in the future stromal region

abnormal cornea morphology ( J:48079 )

• the arrangement of cells within the cornea is disorganized

abnormal cornea endothelium morphology ( J:56425 )

• fails to differentiate normally

abnormal cornea epithelium morphology ( J:56425 )

• cells become enlarged and separated from one another by microvilli lined spaces

increased cornea epithelium thickness ( J:56425 )

• comes to be composed of more cell layers than normal

small lens ( J:56425 )

• significantly reduced in size

eyelids open at birth ( J:48079 )

• the eyelids are not fused at birth

abnormal nasolacrimal duct morphology ( J:107208 )

• at E18.5, the lacrimal ducts are distended with individual buds shorter and wider than in wild-type mice

• the length of the ducts and number of terminal buds are reduced compared to in wild-type mice

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:57677 )

• major malformations in the branchial arch arteries and heart are found in all double heterozygotes

abnormal fourth pharyngeal arch artery morphology ( J:57677 )

• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4

aortic arch coarctation ( J:57677 )

• coarctation of the arch of the aorta is found at E11.5 and in newborns (3 out of 5 and 6 out of 11, respectively)

interrupted aortic arch ( J:57677 )

• at E13.5 and 16.5 interruption of the arch of the aorta is found (2 out of 3 and 2 out of 6 respectively)

patent ductus arteriosus ( J:57677 )

• the ductus arteriosus connecting the aorta to the pulmonary artery fails to close in all newborns

ventricular septal defect ( J:57677 )

• ventricular septal defects are found at E13.5, E16.5 and in newborns (2 out of 6; 2 out of 3; 8 out of 11, respectively)

abnormal semilunar valve morphology ( J:57677 )

abnormal aortic valve morphology ( J:57677 )

• dysplasia

abnormal aortic valve cusp morphology ( J:57677 )

• in newborns the normal number of leaflets is found but these are thickened and partially fused (8 out of 11)

thick aortic valve cusps ( J:57677 )

abnormal pulmonary valve morphology ( J:57677 )

• dysplasia

abnormal pulmonary valve cusp morphology ( J:57677 )

• in newborns the normal number of leaflets is found but these are thickened and partially fused (8 out of 11)

thick pulmonary valve cusps ( J:57677 )

ovary hemorrhage ( J:105944 )

♀ • large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host

intracranial hemorrhage ( J:48079 )

• at E14.5 the integrity of some blood vessels in the brain is disrupted and the surrounding area is acellular

craniofacial

abnormal pharyngeal arch artery morphology ( J:57677 )

• major malformations in the branchial arch arteries and heart are found in all double heterozygotes

abnormal fourth pharyngeal arch artery morphology ( J:57677 )

• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4

abnormal craniofacial bone morphology ( J:48079 )

small basisphenoid bone ( J:48079 )

• in newborns the basisphenoid bone is reduced and malformed

absent neurocranium ( J:48079 )

• in newborns the calvarial bones are absent

abnormal maxillary zygomatic process morphology ( J:48079 )

• the zygomatic process is enlarged and fused to the mandible

enlarged maxillary zygomatic process ( J:48079 )

homeostasis/metabolism

hydrops fetalis ( J:57677 )

• 30% of embryos collected between E17.5 and E18.5 are dead or edematous (5 out of 15)

limbs/digits/tail

abnormal tarsal bone morphology ( J:48079 )

• in newborns the digits are thinner than normal with smaller ossification centers

abnormal humerus morphology ( J:48079 )

abnormal deltoid tuberosity morphology ( J:48079 )

• in newborns the deltoid process of the humerus is misshapen

nervous system

intracranial hemorrhage ( J:48079 )

• at E14.5 the integrity of some blood vessels in the brain is disrupted and the surrounding area is acellular

hydrocephaly ( J:48079 )

• by E11.5 the brain size is clearly increased in mutants

• at E14.5 the integrity of some blood vessels in the brain is disrupted and the surrounding area is acellular

endocrine/exocrine glands

ovary hemorrhage ( J:105944 )

♀ • large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host

abnormal lacrimal gland morphology ( J:107208 )

• at E18.5, lactimal ducts are distended; the overall length of the gland duct is significantly reduced

abnormal exorbital lacrimal gland morphology ( J:107208 )

• at E18.5, the exorbital lobe is severely reduced compared to in wild-type mice

• significantly fewer branches and terminal buds are observed within the exorbital lobe

absent intraorbital lacrimal gland ( J:107208 )

• at E18.5, the intra-orbital lacrimal gland is absent

abnormal lacrimal gland branching morphogenesis ( J:107208 )

• at E16.5, branches of the lacrimal gland are shorter and wider with fewer terminal buds than in wild-type mice

• lacrimal gland explants have fewer branches with terminal buds that are longer and wider than in wild-type lacrimal explants

• however, lacrimal gland epithelium differentiation is normal

abnormal ovary morphology ( J:105944 )

♀ • ovaries lack distinct cortex and medulla regions as in wild-type ovaries

♀ • granulosa and thecal cell layers as well as the basement membrane separating the two are less well defined than in wild-type mice

♀ • after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice

♀ • by week 8 after engraftment into a wild-type host, 1 of 4 ovaries contain Seroli cells tubule-like structures

abnormal ovarian cortex morphology ( J:105944 )

♀ • at E18.5, mutant ovaries lack a distinct cortex region

abnormal ovarian follicle morphology ( J:105944 )

♀ • by 8 weeks of engraftment into a wild-type host, remaining healthy follicles are larger than in wild-type mice

impaired ovarian folliculogenesis ( J:105944 )

♀ • when ovaries are transplanted into a wild-type host, follicles fail to progress beyond the pre-antral/early antral stages

polyovular ovarian follicle ( J:105944 )

♀ • after 8 weeks, ovaries engrafted into a wild-type host often contain polyovular follicles and contain regions of cells not organized into follicles-like structures unlike in wild-type mice

abnormal ovarian medulla morphology ( J:105944 )

♀ • at E18.5, mutant ovaries lack a distinct medulla region

small ovary ( J:105944 )

♀ • at E18.5, mutant ovaries are smaller than wild-type

ovary cyst ( J:105944 )

♀ • large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host

disorganized testis cords ( J:105944 )

♂ • seminiferous cords are present but interspersed with regions of disorganized cells where no cords are apparent

small testis ( J:105944 )

♂

abnormal testis tunica albuginea morphology ( J:105944 )

♂ • at E18.5, testes exhibit a reduced tunica albuginea

abnormal lacrimal gland physiology ( J:107208 )

• lacrimal gland mesenchyme is insensitive to Bmp7 treatment unlike wild-type mesenchyme

• however, lacrimal gland epithelium proliferation in response to FGF is normal

renal/urinary system

duplex kidney ( J:60834 )

• seen in 1 of 49 mice

bifid ureter ( J:60834 )

• seen in 1 of 49 mice

cellular

patent ductus arteriosus ( J:57677 )

• the ductus arteriosus connecting the aorta to the pulmonary artery fails to close in all newborns

decreased oocyte number ( J:105944 )

♀ • ovaries contain fewer germ cells that are found in clusters scattered throughout the ovary unlike in wild-type mice

oocyte degeneration ( J:105944 )

♀ • after 8 weeks of engraftment into a wild-type host, ovaries display oocyte degeneration or loss

abnormal primordial germ cell migration ( J:105944 )

• between E10.5 and E11.5, fewer than normal primordial germ cells migrate out of the hindgut resulting in fewer germ cells entering the developing gonads

• however, germ cell attractants are normally expressed

growth/size/body

ovary cyst ( J:105944 )

♀ • large follicle cysts, several of which are hemorrhagic, develop when ovaries are engrafted into a wild-type host

abnormal ovarian bursa morphology ( J:105944 )

♀ • at E18.5, no bursa membrane can be detected, unlike in wild-type ovaries

Genotype
MGI:3811484

ht3

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺
• Genetic Background: 129S6/SvEvTac-Foxc1^tm1Blh

vision/eye

abnormal anterior eye segment morphology ( J:61775 )

• Background Sensitivity: incidence and severity of anterior segment abnormalities varies with strain background

• 2 of 8 mice had obvious anterior segment abnormalities at 11 months of age

abnormal iridocorneal angle ( J:61775 )

• most eyes contain morphologically normal and abnormal regions of the iridocorneal angle

• abnormalities include large blood vessels and iris strands

abnormal canal of Schlemm morphology ( J:61775 )

• small or absent

• in some areas the canal of Schlemm is absent, in others it is relatively normal but contains fewer giant vacuoles, and in still others it has a normal appearance

abnormal trabecular meshwork morphology ( J:61775 )

• areas may be hypoplastic or absent

• in some places the trabecular meshwork appears compressed

• some areas where the trabecular meshwork is absent contain cells that resemble mesenchymal precursor cells

• some abnormal areas show a decrease in the amount of extracellular matrix components present

abnormal placement of pupils ( J:61775 )

• at 11 months of age in 2 of 8 mice, the left pupil in was eccentric

irregularly shaped pupil ( J:61775 )

• seen in the left eyes of 2 of 8 mice at 11 months of age

abnormal cornea morphology ( J:61775 )

• at 11 months of age in 1 of 8 mice in the right eye, the focal region of the peripheral cornea was opaque and resemble sclera

Genotype
MGI:3655827

ht4

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺
• Genetic Background: B6.Cg-Foxc1^tm1Blh

vision/eye

abnormal aqueous drainage system morphology ( J:82280 )

• pigmented mice had mild developmental defects than compared to albino Tyr^c-2J/Tyr^c-2J, Foxc1^tm1Blh /Foxc1⁺ mice

hypoplastic trabecular meshwork ( J:82280 )

• mild hypoplasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
buphthalmos		DOID:11211	OMIM:231300	J:82280

Genotype
MGI:3811488

ht5

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

vision/eye

abnormal anterior eye segment morphology ( J:61775 )

• Background Sensitivity: incidence and severity of anterior segment abnormalities varies with strain background

abnormal iridocorneal angle ( J:61775 )

• most eyes contain morphologically normal and abnormal regions of the iridocorneal angle

• abnormalities include large blood vessels and iris strands

abnormal canal of Schlemm morphology ( J:61775 )

• small or absent

abnormal trabecular meshwork morphology ( J:61775 )

• areas may be hypoplastic or absent

• in some places the trabecular meshwork appears compressed

abnormal iris morphology ( J:61775 )

• 1 of 20 mice had abnormal processes extending from the iris

abnormal iris pigment epithelium ( J:61775 )

• thin

abnormal placement of pupils ( J:61775 )

• eccentric pupil present in 1 of 20 mice

irregularly shaped pupil ( J:61775 )

• seen in 1 of 20 mice

iris hypoplasia ( J:61775 )

• hypoplastic development

iris stroma hypoplasia ( J:61775 )

• thin

pigmentation

abnormal iris pigment epithelium ( J:61775 )

• thin

Genotype
MGI:3811486

ht6

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

vision/eye

vision/eye phenotype ( J:61775 )

N • despite abnormalities intraocular pressure is not increased

abnormal anterior eye segment morphology ( J:61775 )

• Background Sensitivity: incidence and severity of anterior segment abnormalities varies with strain background

• at N2 4 of 12 mice had anterior segment abnormalities

• at N3 and higher generations, 20 of 21 mice had anterior segment abnormalities

• 17 of 24 affected mice had abnormalities in both eyes

abnormal iridocorneal angle ( J:61775 )

• most eyes contain morphologically normal and abnormal regions of the iridocorneal angle

• abnormalities include large blood vessels and iris strands

abnormal canal of Schlemm morphology ( J:61775 )

• small or absent

abnormal trabecular meshwork morphology ( J:61775 )

• areas may be hypoplastic or absent

• in some places the trabecular meshwork appears compressed

• some areas where the trabecular meshwork is absent contain cells that resemble mesenchymal precursor cells

abnormal line of Schwalbe morphology ( J:61775 )

• displaced and/or enlarged

abnormal iris morphology ( J:61775 )

• tears are present

abnormal placement of pupils ( J:61775 )

• severely misplaced in some mice

irregularly shaped pupil ( J:61775 )

• some mice had irregular pupils with normal locations others have irregular pupils with iris tears

abnormal cornea morphology ( J:61775 )

• scleralization of the peripheral cornea

anterior iris synechia ( J:61775 )

• iris strands are frequently attached to the cornea

cataract ( J:61775 )

Genotype
MGI:3811485

ht7

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺
• Genetic Background: involves: 129S6/SvEvTac * CAST/Ei

vision/eye

vision/eye phenotype ( J:61775 )

N • Background Sensitivity: unlike mice on other backgrounds no clinical anterior segment abnormalities are seen in mice crossed onto the CAST/Ei background

abnormal iridocorneal angle ( J:61775 )

• most eyes contain morphologically normal and abnormal regions of the iridocorneal angle

• abnormalities include large blood vessels and iris strands

abnormal canal of Schlemm morphology ( J:61775 )

• small or absent

abnormal trabecular meshwork morphology ( J:61775 )

• areas may be hypoplastic or absent

• in some places the trabecular meshwork appears compressed

• some areas where the trabecular meshwork is absent contain cells that resemble mesenchymal precursor cells

Genotype
MGI:4437878

ht8

• Allelic Composition: Foxc1^hith/Foxc1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

nervous system

abnormal neuron differentiation ( J:157301 )

• at E14.5, the number of intermediate progenitor cells is decreased compared to in wild-type mice

abnormal neuron proliferation ( J:157301 )

• at E14.5, neuron proliferation in the cortex is reduced compared to in wild-type mice

abnormal forebrain morphology ( J:157301 )

• at E12.5, dorsal forebrain lengthening is observed unlike in wild-type mice

• at E14.5, the dorsal forebrain is longer and thinner than in wild-type mice

• however, treatment with all-trans retinoic acid restores forebrain morphology

abnormal cerebral cortex morphology ( J:157301 )

• at E18.5

abnormal stratification in cerebral cortex ( J:157301 )

• at E18.5, cortical layers are disorganized compared to in wild-type mice

abnormal brain meninges morphology ( J:157301 )

• at E14.5, the lateral meninges are reduced and the dorsal meninges are absent unlike in wild-type mice

cellular

abnormal neuron differentiation ( J:157301 )

• at E14.5, the number of intermediate progenitor cells is decreased compared to in wild-type mice

abnormal neuron proliferation ( J:157301 )

• at E14.5, neuron proliferation in the cortex is reduced compared to in wild-type mice

Genotype
MGI:3798681

cn9

• Allelic Composition: Foxc1^tm1Tsku/Foxc1^tm1Blh; Tg(Tek-cre)1Rwng/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

cellular

abnormal cell migration ( J:131323 )

• isolated pulmonary microvascular endothelial cells exhibit a significant reduction in chemotactic migration towards Cxcl12

Genotype
MGI:3655825

cx10

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺; Tyr^c-2J/Tyr^c-2J
• Genetic Background: B6.Cg-Tyr^c-2J Foxc1^tm1Blh

vision/eye

abnormal aqueous drainage system morphology ( J:82280 )

• albino mice had severe and more extensive angle developmental defects than pigmented Foxc1^tm1Blh /Foxc1⁺ mice

absent Schlemm's canal ( J:82280 )

• a small or absent Schlemm's canal

abnormal trabecular meshwork morphology ( J:82280 )

• basal lamina extending from the cornea over the trabecular meshwork

iris synechia ( J:82280 )

• broad synechiae occupies the region where the trabecular meshwork is normally located

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
buphthalmos		DOID:11211	OMIM:231300	J:82280

Genotype
MGI:3811363

cx11

• Allelic Composition: Foxc1^tm1Blh/Foxc1^tm1Blh; Foxc2^tm1Blh/Foxc2⁺
• Genetic Background: involves: 129S6/SvEvTac

embryo

embryo phenotype ( J:91443 )

N • somites develop normally

Genotype
MGI:3811359

cx12

• Allelic Composition: Foxc1^tm1Blh/Foxc1^tm1Blh; Foxc2^tm1Blh/Foxc2^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac

embryo

embryo phenotype ( J:91443 )

N • despite the lack of somites, proliferation and apoptosis rates of paraxial mesoderm are normal

abnormal mesonephros morphology ( J:91443 )

• at E9.5, mesonephric tissue is expanded and disorganized compared to in wild-type mice

abnormal somite development ( J:91443 )

• mice exhibit ectopic expression of intermediate mesoderm markers leading to increased lateralization of somites

absent somites ( J:91443 )

• mice lack somites

Genotype
MGI:3811361

cx13

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺; Foxc2^tm1Blh/Foxc2^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac

embryo

abnormal mesonephros morphology ( J:91443 )

• at E9.5, mesonephric tissue is expanded and disorganized compared to in wild-type mice

abnormal somite shape ( J:91443 )

• somites are very narrow and irregular

Genotype
MGI:2170676

cx14

• Allelic Composition: Foxc1^tm1Blh/Foxc1^tm1Blh; Foxc2^tm1Blh/Foxc2^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:71693 )

• double homozygotes die at ~E9.0-E9.5 with a much more severe phenotype than that of either single homozygote alone

cardiovascular system

abnormal vascular development ( J:71693 )

• at E9.0, most blood vessels are still organized into primitive plexi; no blood vessels have sprouted from the dorsal aorta

abnormal dorsal aorta morphology ( J:71693 )

dilated dorsal aorta ( J:71693 )

• at E9.0, double homozygotes exhibit a dilated dorsal aorta with blood accumulated probably as a result of a weakly beating heart

disorganized myocardium ( J:71693 )

• at E9.0, double homozygotes show a disorganized myocardium

small heart ( J:71693 )

• at E9.0, double homozygotes display a small heart

enlarged pericardium ( J:71693 )

• at E9.5, double homozygotes occasionally display an enlarged pericardial sac

abnormal heartbeat ( J:71693 )

• at E9.0, double homozygotes display a weak heartbeat

craniofacial

small first pharyngeal arch ( J:71693 )

• at E9.0, double homozygotes have very small first branchial arches

absent second pharyngeal arch ( J:71693 )

• at E9.0, double homozygotes completely lack a second branchial arch and have a very small first branchial arch

• dense accumulations of mesenchymal cells with pycnotic nuclei are detected in place of a second branchial arch

embryo

small first pharyngeal arch ( J:71693 )

• at E9.0, double homozygotes have very small first branchial arches

absent second pharyngeal arch ( J:71693 )

• at E9.0, double homozygotes completely lack a second branchial arch and have a very small first branchial arch

• dense accumulations of mesenchymal cells with pycnotic nuclei are detected in place of a second branchial arch

decreased embryo size ( J:71693 )

• at E9.5, double homozygotes are significantly smaller than wild-type embryos

absent paraxial mesoderm ( J:71693 )

• at E9.0, double homozygotes display absence of segmented paraxial mesoderm

head mesenchyme hypoplasia ( J:71693 )

• sparse mesenchyme

incomplete rostral neuropore closure ( J:71693 )

• at E9.5, double homozygotes usually display an open anterior neural tube

abnormal pharyngeal pouch morphology ( J:71693 )

• at E9.0, sections at the level of the first branchial arch reveal ectopic epithelial tubes that may represent endoderm that would have formed branchial pouches

abnormal dorsal-ventral polarity of the somites ( J:71693 )

• at E9.5, double homozygotes fail to establish A/P domains in the anterior presomitic mesoderm

absent somites ( J:71693 )

• at E9.5, double homozygotes display absence of segmented, epithelialized somites, including dermamyotome, in the trunk region

• absence of the most anterior somites (1-8) indicates a defect in early somitogenesis

abnormal vitelline vascular remodeling ( J:71693 )

• at E9.0, double mutant yolk sacs contain only enlarged vessels in a primitive plexus that has undergone very little remodeling; no small blood vessels are present

growth/size/body

decreased embryo size ( J:71693 )

• at E9.5, double homozygotes are significantly smaller than wild-type embryos

abnormal head development ( J:71693 )

• at E9.0, double homozygotes show a disorganized head structure, including sparse mesenchyme and enlarged blood vessels

head mesenchyme hypoplasia ( J:71693 )

• sparse mesenchyme

nervous system

incomplete rostral neuropore closure ( J:71693 )

• at E9.5, double homozygotes usually display an open anterior neural tube

muscle

disorganized myocardium ( J:71693 )

• at E9.0, double homozygotes show a disorganized myocardium

Genotype
MGI:2170671

cx15

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺; Foxc2^tm1Blh/Foxc2⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:57677 )

• most embryos die between E14.5 and birth

• double heterozygotes shown signs of cardiac failure between E13.5 and E15.5

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:57677 )

• major malformations in the branchial arch arteries and heart are found in all double heterozygotes

abnormal fourth pharyngeal arch artery morphology ( J:57677 )

• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4

aortic arch coarctation ( J:57677 )

• coarctation of the arch of the aorta is found in 8 of 17 embryos at E13.5

interrupted aortic arch, type b ( J:57677 )

• at E12.5 and 13.5 type B interruption of the arch of the aorta is seen

decreased angiogenesis ( J:57677 )

• the number of coronary vessels is decreased in embryos examined between E15.5 and E17.5

abnormal superior vena cava morphology ( J:57677 )

• in embryos collected between E13.5 and E15.5 the superior caval veins are overexpanded

ventricle myocardium hypoplasia ( J:57677 )

• the thickness of the myocardium of the ventricles is decreased in all double heterozygotes between E13.5 and E17.5

trabecula carnea hypoplasia ( J:57677 )

• the extent of trabeculations of the ventricles is decreased in all double heterozygotes between E13.5 and E17.5

perimembraneous ventricular septal defect ( J:57677 )

• the membraneous portion of the ventricular septum fails to fuse at E13.5 (15 out of 17)

abnormal aortic valve morphology ( J:57677 )

• at E13.5 dysplasia of the semilunar valves is found (8 out of 17)

thick aortic valve cusps ( J:57677 )

• the leaflets are thickened and partially fused

abnormal pulmonary valve morphology ( J:57677 )

• at E13.5 dysplasia of the semilunar valves is found (8 out of 17)

thick pulmonary valve cusps ( J:57677 )

• the leaflets are thickened and partially fused

cornea vascularization ( J:61775 )

homeostasis/metabolism

hydrops fetalis ( J:57677 )

• 65% of embryos collected between E13.5 and E15.5 are edematous

liver/biliary system

enlarged liver ( J:57677 )

• the fetal liver is enlarged and engorged with blood

renal/urinary system

hydronephrosis ( J:60834 )

• 26% of newborn double heterozygotes display hydronephrosis

renal hypoplasia ( J:60834 )

• 7 of 19 newborn double heterozygotes have hypoplastic kidneys (less than 3/4 of wild-type length)

• hypoplastic kidneys are either unilateral (71%) or bilateral (29%)

absent kidney ( J:60834 )

• 5% of newborn double heterozygotes show renal agenesis

duplex kidney ( J:60834 )

• 1 of 19 newborn double heterozygotes had a duplex kidney and double ureters

double ureter ( J:60834 )

• 1 of 19 newborn double heterozygotes had a duplex kidney and double ureters

hydroureter ( J:60834 )

• 13 of 19 double heterozygotes have a single hydroureter

• hydroureter is either unilateral (85%) or bilateral (15%)

abnormal branching involved in ureteric bud morphogenesis ( J:60834 )

• at E10.5, 2 of 3 double heterozygotes show a much broader outgrowth of the ureteric bud

ectopic ureteric bud ( J:60834 )

• at E11.0, 3 of 4 double heterozygotes exhibit an ectopic ureteric bud

skeleton

skeleton phenotype ( J:57677 )

N • no gross malformations of the vertebral column, ribs, or skull are found

embryo

abnormal pharyngeal arch artery morphology ( J:57677 )

• major malformations in the branchial arch arteries and heart are found in all double heterozygotes

abnormal fourth pharyngeal arch artery morphology ( J:57677 )

• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4

abnormal mesonephros morphology ( J:60834 )

• double heterozygotes display extra mesonephric tubules distributed caudally between somites 16 and 23

vision/eye

abnormal iridocorneal angle ( J:61775 )

• abnormalities similar to those in Foxc1^tm1Blh heterozygotes are seen

abnormal canal of Schlemm morphology ( J:61775 )

• small or absent

abnormal trabecular meshwork morphology ( J:61775 )

• areas may be hypoplastic or absent

abnormal ciliary body morphology ( J:61775 )

• intermittent abnormalities are seen

abnormal iris morphology ( J:61775 )

• more severely affected than in either single heterozygote

iris stroma hypoplasia ( J:61775 )

• almost completely absent in some areas

abnormal cornea morphology ( J:61775 )

• corneal ulcers and immune cell infiltrates are present in some eyes

cornea vascularization ( J:61775 )

cornea ulcer ( J:61775 )

• present in some eyes

eyelids open at birth ( J:61775 )

• in some cases

muscle

ventricle myocardium hypoplasia ( J:57677 )

• the thickness of the myocardium of the ventricles is decreased in all double heterozygotes between E13.5 and E17.5

trabecula carnea hypoplasia ( J:57677 )

• the extent of trabeculations of the ventricles is decreased in all double heterozygotes between E13.5 and E17.5

craniofacial

abnormal pharyngeal arch artery morphology ( J:57677 )

• major malformations in the branchial arch arteries and heart are found in all double heterozygotes

abnormal fourth pharyngeal arch artery morphology ( J:57677 )

• in 2 of 3 embryos examined on E10.5 and 11.5 a blister like defect is seen on the wall of left arch artery 4

growth/size/body

enlarged liver ( J:57677 )

• the fetal liver is enlarged and engorged with blood

Genotype
MGI:3622548

cx16

• Allelic Composition: Foxc1^tm1Blh/Foxc1^tm1Blh; Foxc2^tm1Blh/Foxc2⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:71693 )

• mutant embryos die at ~E11.5

cardiovascular system

cardiovascular system phenotype ( J:71693 )

N • at E9.5, mutant embryos display no obvious defects in remodeling of blood vessels; however, an in-depth phenotype analysis is warranted

Genotype
MGI:3622549

cx17

• Allelic Composition: Foxc1^tm1Blh/Foxc1⁺; Foxc2^tm1Blh/Foxc2^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:71693 )

• mutant embryos die at ~E10.5, with a more severe phenotype than that of double heterozygotes or either single homozygote alone

cardiovascular system

abnormal vascular development ( J:71693 )

• at E10.5, mutant embryos show extensive defects in the remodeling of blood vessels in the head and body

abnormal pharyngeal arch artery morphology ( J:71693 )

• at E10.5, mutant embryos exhibit variable and multiple branchial arch artery abnormalities, including an enlarged third BA artery with an ectopic branch, thin BA arteries, and generally disorganized BA arteries

enlarged third pharyngeal arch artery ( J:71693 )

• enlarged in some mice

craniofacial

abnormal pharyngeal arch artery morphology ( J:71693 )

• at E10.5, mutant embryos exhibit variable and multiple branchial arch artery abnormalities, including an enlarged third BA artery with an ectopic branch, thin BA arteries, and generally disorganized BA arteries

enlarged third pharyngeal arch artery ( J:71693 )

• enlarged in some mice

absent second pharyngeal arch ( J:71693 )

• at E10.5, mutant embryos lack a second branchial arch

embryo

abnormal pharyngeal arch artery morphology ( J:71693 )

• at E10.5, mutant embryos exhibit variable and multiple branchial arch artery abnormalities, including an enlarged third BA artery with an ectopic branch, thin BA arteries, and generally disorganized BA arteries

enlarged third pharyngeal arch artery ( J:71693 )

• enlarged in some mice

absent second pharyngeal arch ( J:71693 )

• at E10.5, mutant embryos lack a second branchial arch

abnormal somite shape ( J:71693 )

• at E10.5, mutant embryos have abnormally shaped somites

decreased somite size ( J:71693 )

• at E10.5, mutant embryos have abnormally small somites