Phenotypes associated with this allele

• Allele Symbol: Foxc2^tm1Miu
• Allele Name: targeted mutation 1, Naoyuki Miura
• Allele ID: MGI:1857740
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxc2^tm1Miu/Foxc2^tm1Miu	involves: 129P2/OlaHsd * C57BL/6	MGI:2169410
hm2	Foxc2^tm1Miu/Foxc2^tm1Miu	involves: 129P2/OlaHsd * C57BL/6J * ICR	MGI:3625982
ht3	Foxc2^tm1Miu/Foxc2^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:3622353
cx4	Foxc2^tm1Miu/Foxc2^tm1Miu Pax1^tm2Neu/Pax1^tm2Neu	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:2169357
cx5	Ednra^tm1Ywa/Ednra^tm1Ywa Foxc2^tm1Miu/Foxc2^tm1Miu	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3628465

Genotype
MGI:2169410

hm1

• Allelic Composition: Foxc2^tm1Miu/Foxc2^tm1Miu
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:55316 )

• mutants die from respiratory compromise within 10 minutes of birth

embryonic lethality during organogenesis, incomplete penetrance ( J:55316 )

• about half of the homozygotes died before birth

• dead embryos were first detected on E12.5

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:55316 )

• at E12.5 the left arch artery 4 regresses in most mutants

abnormal third pharyngeal arch artery morphology ( J:55316 )

• at E12.5 the proximal segment of the left arch artery 3 is diminished in a few cases

abnormal aortic arch morphology ( J:55316 )

• all newborns have abnormalities in the arch of the aorta

aortic arch coarctation ( J:55316 )

• coarctation of the arch of the aorta occurs in 4 of 12 newborns

interrupted aortic arch, type b ( J:55316 )

• in 5 out of 12 mutants, interuption of the aortic arch between the left common carotid artery and the left subclavian artery is seen

ventricular septal defect ( J:55316 )

• in newborns a tiny defect in the ventricular septum is found

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:55316 )

• at E12.5 the left arch artery 4 regresses in most mutants

abnormal third pharyngeal arch artery morphology ( J:55316 )

• at E12.5 the proximal segment of the left arch artery 3 is diminished in a few cases

abnormal craniofacial bone morphology ( J:55316 )

abnormal supraoccipital bone morphology ( J:55316 )

• ossification of the supraoccipital bone is totally impaired

• this bone is replaced with a cartilaginous mass

abnormal sphenoid bone morphology ( J:55316 )

abnormal basisphenoid bone morphology ( J:55316 )

• the basisphenoid bone is slightly shortened craniocaudally

abnormal alisphenoid bone morphology ( J:55316 )

• the mediocaudal region of the alisphenoid bone is missing

abnormal presphenoid bone morphology ( J:55316 )

• ossification of the presphenoid bone is missing or delayed

abnormal pterygoid process morphology ( J:55316 )

• the pterygoid bone process is present but deformed and shifted laterally

abnormal palatine bone horizontal plate morphology ( J:55316 )

• the palatal process is present but deformed and shifted laterally

abnormal middle ear ossicle morphology ( J:55316 )

abnormal malleus morphology ( J:55316 )

• the malleus is fused to the incus

gonial bone hypoplasia ( J:55316 )

malleus hypoplasia ( J:55316 )

absent soft palate ( J:55316 )

• the soft palate is missing

cleft secondary palate ( J:55316 )

• all newborns have a complete cleft of the secondary palate

• the palatal shelf is shifted laterally

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:55316 )

abnormal malleus morphology ( J:55316 )

• the malleus is fused to the incus

gonial bone hypoplasia ( J:55316 )

malleus hypoplasia ( J:55316 )

abnormal otic vesicle development ( J:55316 )

• ossification of the otic vesicle is impaired

respiratory system

atelectasis ( J:55316 )

• neonates have a collapsed lung

skeleton

abnormal craniofacial bone morphology ( J:55316 )

abnormal supraoccipital bone morphology ( J:55316 )

• ossification of the supraoccipital bone is totally impaired

• this bone is replaced with a cartilaginous mass

abnormal sphenoid bone morphology ( J:55316 )

abnormal basisphenoid bone morphology ( J:55316 )

• the basisphenoid bone is slightly shortened craniocaudally

abnormal alisphenoid bone morphology ( J:55316 )

• the mediocaudal region of the alisphenoid bone is missing

abnormal presphenoid bone morphology ( J:55316 )

• ossification of the presphenoid bone is missing or delayed

abnormal pterygoid process morphology ( J:55316 )

• the pterygoid bone process is present but deformed and shifted laterally

abnormal palatine bone horizontal plate morphology ( J:55316 )

• the palatal process is present but deformed and shifted laterally

abnormal middle ear ossicle morphology ( J:55316 )

abnormal malleus morphology ( J:55316 )

• the malleus is fused to the incus

gonial bone hypoplasia ( J:55316 )

malleus hypoplasia ( J:55316 )

rib fusion ( J:55575 )

• mice occasionally exhibit fusion of the proximal parts of the ribs unlike in wild-type mice

abnormal vertebral arch morphology ( J:55575 )

• the dorsal portion of the neural arch in the atlas and thoracic vertebrae is abnormal

spina bifida occulta ( J:55316 )

abnormal vertebral body morphology ( J:55575 , J:55316 )

• ossification centers in the vertebral bodies of the cervical region are absent and irregularly formed in the thoracolumbar region compared to in wild-type mice (J:55575)

• the annuli fibrosi is not normally generated (J:55575)

• in the cervical region only the ossification center of the atlas could be found (J:55316)

• the transverse foramen, through which the vertebral artery passes, is not formed (J:55316)

• the cartilaginous condensation of the lamina of the neural arches in the cervical region is split at the midline (J:55316)

• in the thoracolumbar region the ossification centers are small, irregularly aligned and split (J:55316)

small vertebral body ( J:55575 )

short vertebral body ( J:55316 )

• the vertebral bodies appeared shorter

absent cartilage ( J:55316 )

• the pterygoquadrate cartilage is absent

abnormal bone ossification ( J:55316 )

• ossification of a number of bones is impaired

• in some bone ossification centers are absent

nervous system

spina bifida occulta ( J:55316 )

embryo

abnormal fourth pharyngeal arch artery morphology ( J:55316 )

• at E12.5 the left arch artery 4 regresses in most mutants

abnormal third pharyngeal arch artery morphology ( J:55316 )

• at E12.5 the proximal segment of the left arch artery 3 is diminished in a few cases

spina bifida occulta ( J:55316 )

digestive/alimentary system

abnormal palatine bone horizontal plate morphology ( J:55316 )

• the palatal process is present but deformed and shifted laterally

absent soft palate ( J:55316 )

• the soft palate is missing

cleft secondary palate ( J:55316 )

• all newborns have a complete cleft of the secondary palate

• the palatal shelf is shifted laterally

growth/size/body

abnormal palatine bone horizontal plate morphology ( J:55316 )

• the palatal process is present but deformed and shifted laterally

absent soft palate ( J:55316 )

• the soft palate is missing

cleft secondary palate ( J:55316 )

• all newborns have a complete cleft of the secondary palate

• the palatal shelf is shifted laterally

Genotype
MGI:3625982

hm2

• Allelic Composition: Foxc2^tm1Miu/Foxc2^tm1Miu
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * ICR

renal/urinary system

glomerulus hemorrhage ( J:106710 )

• distended glomerular capillary loops are blood-filled at E18.5

abnormal podocyte morphology ( J:106710 )

• at E18.5, podocytes fail to form foot processes and slit diaphragms, and instead remain columnar and partially connected by adherence junctions (typical features of immature podocytes)

absent podocyte foot process ( J:106710 )

• at E18.5, podocytes lack foot processes

absent podocyte slit diaphragm ( J:106710 )

• at E18.5, podocytes lack slit diaphragms

abnormal renal glomerulus basement membrane morphology ( J:106710 )

• GBM is deposited normally during early development but fails to mature during the cup-shaped and capillary loop stages through the incorporation of Col4a3, Col4a4 and Col4a5 chains

abnormal renal glomerulus morphology ( J:106710 )

• abnormally shaped glomeruli at E18.5

• differentiation of podocytes and endothelial cells is arrested before the capillary loop stage of glomerular development

absent glomerular endothelium fenestra ( J:106710 )

• at E18.5, glomerular endothelial cells lack fenestrations

decreased glomerular capillary number ( J:106710 )

• fewer than normal capillary loops at E18.5

dilated glomerular capillary ( J:106710 )

• dilated glomerular capillary loops at E18.5

abnormal glomerular mesangium morphology ( J:106710 )

• abnormal organization of the glomerular mesangium at E18.5

abnormal mesangial cell morphology ( J:106710 )

• at E18.5, mesangial cells fail to form a tree-like mesangial core and remain localized in a compact cluster at the center of the glomerular tuft

• mesangial cells fail to make the normal focal contacts with the GBM

decreased renal glomerulus number ( J:106710 )

• reduced numbers of glomeruli at E18.5

small kidney ( J:106710 )

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

cardiovascular system

absent glomerular endothelium fenestra ( J:106710 )

• at E18.5, glomerular endothelial cells lack fenestrations

decreased glomerular capillary number ( J:106710 )

• fewer than normal capillary loops at E18.5

dilated glomerular capillary ( J:106710 )

• dilated glomerular capillary loops at E18.5

glomerulus hemorrhage ( J:106710 )

• distended glomerular capillary loops are blood-filled at E18.5

cellular

abnormal mesangial cell morphology ( J:106710 )

• at E18.5, mesangial cells fail to form a tree-like mesangial core and remain localized in a compact cluster at the center of the glomerular tuft

• mesangial cells fail to make the normal focal contacts with the GBM

Genotype
MGI:3622353

ht3

• Allelic Composition: Foxc2^tm1Miu/Foxc2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

immune system

abnormal lymph circulation ( J:83436 )

• 20 of 25 heterozygotes exhibit lymph reflux from the cisterna chyli into dilated lymphatic channels within the hepatic hilum, mesentery, mesenteric lymph nodes and the intestinal wall through incompetent interlymphangion valves

increased lymph node number ( J:83436 )

• 23 of 25 heterozygotes exhibit a general increase in the number of lymph nodes throughout the body

enlarged lymph nodes ( J:83436 )

• 23 of 25 heterozygotes exhibit a general increase in the size of lymph nodes throughout the body

abnormal thoracic duct morphology ( J:83436 )

• 2 of 25 heterozygotes display a hyperplastic thoracic duct with several tortuous bifurcations

lymphangiectasis ( J:83436 )

• heteroygotes show multiple dilated capsular lymphatics and significantly expanded lymph node sinuses (lymphangiectasia), occupying up to 50% of nodal volume

lymphatic vessel hyperplasia ( J:83436 )

• 22 of 25 heterozygotes display a variable but significant increase in the number and caliber of peripheral and central deep lymphatic collectors and trunks and in the superficial dermal lymphatics

vision/eye

abnormal eye morphology ( J:83436 )

• 3 of 25 heterozygotes display ocular dysplasia

abnormal orbit morphology ( J:83436 )

• 3 of 36 heterozygotes exhibit only a vestigial dysplastic ocular remnant unilaterally, associated with a malformation of the orbit

cornea abrasion ( J:83436 )

• 2 of 25 heterozygotes display focal corneal abrasions

cataract ( J:83436 )

• 3 of 25 heterozygotes with cloudy eyes display unilateral cataracts

ocular distichiasis ( J:83436 )

• 100% of heterozygotes (24/24) display an extra internal row of eyelashes arising from the sebaceous meibomian glands

blepharoptosis ( J:83436 )

• 2 of 25 heterozygotes display ptosis of the eye

eye opacity ( J:83436 )

• 5 of 36 heterozygotes exhibit cloudy eyes

homeostasis/metabolism

periorbital edema ( J:83436 )

• 2 of 25 heterozygotes exhibit periorbital swelling

extremity edema ( J:83436 )

• 2 of 25 heterozygotes exhibit hindlimb swelling

lymphedema ( J:83436 )

• 2 of 25 heterozygotes exhibit hindlimb lymphedema; however, no effusions (chylous or non-chylous) or peripheral edema are observed

cardiovascular system

abnormal lymph circulation ( J:83436 )

• 20 of 25 heterozygotes exhibit lymph reflux from the cisterna chyli into dilated lymphatic channels within the hepatic hilum, mesentery, mesenteric lymph nodes and the intestinal wall through incompetent interlymphangion valves

adipose tissue

increased brown adipose tissue amount ( J:83436 )

• heterozygotes exhibit an increased amount of brown fat deposits

craniofacial

abnormal orbit morphology ( J:83436 )

• 3 of 36 heterozygotes exhibit only a vestigial dysplastic ocular remnant unilaterally, associated with a malformation of the orbit

periorbital edema ( J:83436 )

• 2 of 25 heterozygotes exhibit periorbital swelling

skeleton

abnormal orbit morphology ( J:83436 )

• 3 of 36 heterozygotes exhibit only a vestigial dysplastic ocular remnant unilaterally, associated with a malformation of the orbit

growth/size/body

periorbital edema ( J:83436 )

• 2 of 25 heterozygotes exhibit periorbital swelling

Genotype
MGI:2169357

cx4

• Allelic Composition: Foxc2^tm1Miu/Foxc2^tm1Miu; Pax1^tm2Neu/Pax1^tm2Neu
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:55575 )

• half as many mice as expected are present at E19

skeleton

meningomyelocele ( J:55575 )

• at E18.5, mice exhibit subcutaneous myelomeningocoele unlike in wild-type mice

abnormal costovertebral joint morphology ( J:55575 )

• ribs fail to articulate with the vertebral bodies unlike in wild-type mice

rib fusion ( J:55575 )

• mice occasionally exhibit fusion of the proximal parts of the ribs unlike in wild-type mice

absent intervertebral disk ( J:55575 )

abnormal vertebrae development ( J:55575 )

• the cartilaginous primordial of ventral and dorsal structures of vertebra are not generated

• subdermal connective tissue is expanded but no brown adipose tissue is apparent compared to in wild-type mice

• the connective tissue in the cervical region that surrounds the back musculature fails to fuse at the dorsal midline and the medial portions of the back musculature does not form normally

abnormal vertebral lamina morphology ( J:55575 )

• the laminae of the neural arches are completely lost

abnormal vertebral pedicle morphology ( J:55575 )

• fused

abnormal vertebral body morphology ( J:55575 )

• at E15.5, vertebral bodies are poorly developed and occasionally split unlike in wild-type mice

• the annuli fibrosi is not normally generated at all axial levels

vertebral fusion ( J:55575 )

• mice exhibit a fusion of deformed vertebrae in the cervical, thoracic, and lumbar regions

fusion of atlas and odontoid process ( J:55575 )

• the odontoid process is fused to the atlas but not C2

short vertebral column ( J:55575 )

• the vertebral column is shorter compared to in either single homozygote

• ventral and dorsal structures are lacking or strongly reduced compared to in wild-type mice

abnormal sclerotome morphology ( J:55575 )

• at E9.5 and E11.5, expansion of the sclerotome is impaired due to reduction in mitotic cells in the ventrolateral region of the sclerotome

nervous system

abnormal neural tube morphology ( J:55575 )

• the neural tube is deformed by dorsoventral compression

meningomyelocele ( J:55575 )

• at E18.5, mice exhibit subcutaneous myelomeningocoele unlike in wild-type mice

spina bifida ( J:55575 )

abnormal subarachnoid space development ( J:55575 )

• the presumptive subarachnoid space in the lumbar region is narrower than in single homozygotes and the neural tissue extrudes dorsally

abnormal dorsal root ganglion morphology ( J:55575 )

• shifted dorsally

muscle

abnormal muscle development ( J:55575 )

• the connective tissue in the cervical region that surrounds the back musculature fails to fuse at the dorsal midline and the medial portions of the back musculature does not form normally

abnormal dermomyotome development ( J:55575 )

• the dorsal tips of the dermomyotome are shifted dorsally compared to in wild-type mice

cardiovascular system

abnormal dorsal aorta morphology ( J:55575 )

• the anlagen of the dorsal aorta is shifted dorsally compared to in wild-type mice

growth/size/body

decreased body length ( J:55575 )

• at E18.5, the craniocaudal length of mice is two-thirds of wild-type with strong shortening of the caudal region

embryo

abnormal neural tube morphology ( J:55575 )

• the neural tube is deformed by dorsoventral compression

meningomyelocele ( J:55575 )

• at E18.5, mice exhibit subcutaneous myelomeningocoele unlike in wild-type mice

spina bifida ( J:55575 )

Genotype
MGI:3628465

cx5

• Allelic Composition: Ednra^tm1Ywa/Ednra^tm1Ywa; Foxc2^tm1Miu/Foxc2^tm1Miu
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:102130 )

• double homozygous embryos are viable up to E10.5; however, most of them die at ~E11.5 (i.e. earlier than respective single homozygotes) due to heart failure

cardiovascular system

abnormal dorsal aorta morphology ( J:102130 )

• at E10.5, the dorsal aortae between the second and third branchial arch arteries, and between the third and fourth arch arteries (the ductus caroticus) are closed in double homozygotes

persistent truncus arteriosus ( J:102130 )

• all 5 exceptional surviving double homozygotes (2 at E11.5 and 3 at E12.5) exhibit persistent truncus arteriosus (PTA), without ventricular septal defects (VSD) or type B interruption of the aortic arch (IAA)

• authors speculate that double homozygotes with PTA, VSD and IAA are dead at E10.5 or just after E10.5 and that the small number of double homozygotes that have PTA but not VSD nor IAA stay alive until E11.5 and E12.5

dilated heart atrium ( J:102130 )

• at E11.5, all double homozygotes with impaired aorticopulmonary septation display dilated atria

pericardial edema ( J:102130 )

• at E10.5 and E11.5, double homozygotes exhibit an enlarged pericardial space relative to double heterozygotes or single homozygotes

homeostasis/metabolism

pericardial edema ( J:102130 )

• at E10.5 and E11.5, double homozygotes exhibit an enlarged pericardial space relative to double heterozygotes or single homozygotes