Phenotypes associated with this allele

• Allele Symbol: Dbf
• Allele Name: doublefoot
• Allele ID: MGI:1857644
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dbf/Dbf	involves: 101/H * C3H/HeH	MGI:2167919
ht2	Dbf/Dbf^+	involves: 101/H * C3H/HeH	MGI:2170796
ht3	Dbf/Dbf^+	involves: 101/H * C3H/HeH * M. spretus	MGI:3623001

Genotype
MGI:2167919

hm1

• Allelic Composition: Dbf/Dbf
• Genetic Background: involves: 101/H * C3H/HeH

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:39106 , J:50164 )

• die around E13.5 to E14.5 (J:39106)

• homozygotes do not survive beyond day 15 (J:50164)

limbs/digits/tail

broad limb buds ( J:39106 )

• abnormally wide by E11.5

craniofacial

cranioschisis ( J:39106 )

midline facial cleft ( J:39106 , J:50164 )

• at E12.5 and E13.5, the maxillae fail to grow forward to meet at the midline resulting in a 'split face' (J:39106)

homeostasis/metabolism

edema ( J:39106 )

• seen at E14.5

skeleton

cranioschisis ( J:39106 )

embryo

broad limb buds ( J:39106 )

• abnormally wide by E11.5

growth/size/body

abnormal head morphology ( J:39106 )

• the head tends to bulge in the frontal region and a bleb of clear fluid is seen in the midline

midline facial cleft ( J:39106 , J:50164 )

• at E12.5 and E13.5, the maxillae fail to grow forward to meet at the midline resulting in a 'split face' (J:39106)

Genotype
MGI:2170796

ht2

• Allelic Composition: Dbf/Dbf⁺
• Genetic Background: involves: 101/H * C3H/HeH

mortality/aging

premature death ( J:14233 , J:39106 )

• reduced viability (J:14233)

• heterozygotes that develop hydroencephaly rapidly die (J:39106)

prenatal lethality, incomplete penetrance ( J:39106 )

• fewer than expected heterozygotes at birth

cellular

oligozoospermia ( J:39106 )

♂ • some males have reduced sperm counts: however, this does not correlate with infertility

♂ • mean sperm counts are about half of normal but sperm counts vary widely between individuals

limbs/digits/tail

abnormal limb morphology ( J:50164 )

• limbs are thicker dorsoventrally, this appears to be secondary to formation of extra digits

• limb mesenchyme is disorganized with a larger extracellular matrix volume compared to wild-type

broad limb buds ( J:39106 , J:50164 )

• abnormally wide by E11.5 (J:39106)

• by late E10 limbs appear slightly enlarged along the anterior posterior axis; however, at E13 limb length appears normal (J:50164)

increased autopod size ( J:39106 , J:50164 )

• abnormally broad at E12.5 (J:39106)

• the feet are abnormally broad and the soles appear swollen and abnormally smooth (J:39106)

• by E12 the hand and foot plates are greatly enlarged along the anterior posterior axis exclusively on the preaxial aspect of the limb (J:50164)

abnormal carpal bone morphology ( J:50164 )

• duplication of carpal bones to the same extent as the increase in digit number

• at E15 the carpus and tarsus consist of 2 rows of indistinct, contiguous elements unlike in wild-type where these elements are discrete and readily identifiable

abnormal digit morphology ( J:50164 )

• digits are in a fan-shaped array

• all digits are the same length, lack anteroposterior polarity, and show greater separation than wild-type

• 1 in 4 digits are bifurcated and 1 in 8 mice have an interdigital digit

polydactyly ( J:14233 , J:39106 )

• fore feet have 6 to 9 toes and hind feet have 5 to 8 toes, mostly arranged in a single group although a few mice have toes arranged in 2 groups (J:39106)

polysyndactyly ( J:39106 , J:50164 )

• in some cases 2 or more toes have interdigital webbing (J:39106)

• by E13 condensing models for more than 5 digits are seen on the fore and hind limbs and at E14 interdigital webbing persists (J:50164)

• this webbing persists in some heterozygotes through E17 (J:50164)

abnormal foot pad morphology ( J:50164 )

• enlarged ventral footpad

abnormal tarsal bone morphology ( J:50164 )

• duplication of tarsal bones to the same extent as the increase in digit number

• at E15 the carpus and tarsus consist of 2 rows of indistinct, contiguous elements unlike in wild-type where these elements are discrete and readily identifiable

clubfoot ( J:39106 , J:50164 )

• deformities in the tibia and fibula result in dislocation of the ankle joint such that the ankle bone rather than the toes rest on the ground (J:39106)

• in some cases deformities in the radius and ulna result in dislocation of the wrist joint such that the wrist rests on the ground (J:39106)

• seen mainly in the hind feet in extreme cases heterozygotes walk on the outer border of the ankle (J:50164)

• a few adults also show a slight rotational defect in the forefeet (J:50164)

bowed radius ( J:39106 )

• in some cases the radius is bent

bowed ulna ( J:39106 )

• in some cases the ulna is bent

abnormal hindlimb morphology ( J:39106 )

• appear twisted

abnormal fibula morphology ( J:39106 )

• the tibia and fibula fail to fuse

bowed fibula ( J:39106 , J:50164 )

• bowed, probably the result of shortening of the tibia (J:50164)

abnormal tibia morphology ( J:39106 , J:50164 )

• the tibia and fibula fail to fuse (J:39106)

• the tibia has separate proximal and distal sites of chondrogenesis that fuse by E15 but are poorly aligned (J:50164)

• the tibia curves helically around the longitudinal axis and the distal end makes an incomplete, medially situated articulation (J:50164)

• however, the radius and ulna and the rest of the cartilaginous skeleton are normal (J:50164)

bowed tibia ( J:39106 )

short tibia ( J:50164 )

abnormal tail morphology ( J:50164 )

kinked tail ( J:14233 , J:39106 , J:50164 )

• in most cases kinks are the result of soft tissue abnormalities although in a few mice bony kinks are also present (J:39106)

thick tail ( J:39106 , J:50164 )

craniofacial

abnormal craniofacial morphology ( J:50164 )

• at E13 the cranifacial region appears more bulbous than in wild-type mice

Wormian bones ( J:50164 )

• a supernumerary element (Wormian bone) is found in the anterior fontanelle

wide metopic suture ( J:50164 )

• wider than normal

wide sagittal suture ( J:50164 )

• wider than normal

increased cranium width ( J:14233 , J:39106 , J:50164 )

• broader in the frontal region (J:39106)

• skull is broader and more bulbous (J:50164)

abnormal anterior fontanelle morphology ( J:50164 )

• a supernumerary element (Wormian bone) is found in the anterior fontanelle

abnormal frontal bone morphology ( J:39106 )

• a small gap between the frontal bones filled with an interfrontal bone is commonly seen

broad snout ( J:50164 )

• broad snout

growth/size/body

broad snout ( J:50164 )

• broad snout

decreased embryo size ( J:50164 )

• seen at E13

decreased body size ( J:14233 , J:39106 )

decreased body weight ( J:39106 )

• weight is similar at birth but by 18 days of age heterozygotes weigh about 25% less than wild-type littermates

nervous system

hydrocephaly ( J:14233 , J:39106 )

• seen in some but not all heterozygotes (J:14233)

• some heterozygotes develop hydroencephaly at any age between 2-3 weeks and a few months (J:39106)

abnormal diencephalon morphology ( J:50164 )

• at E10 a midline bulge is visible in the roof of the diencephalon

reproductive system

oligozoospermia ( J:39106 )

♂ • some males have reduced sperm counts: however, this does not correlate with infertility

♂ • mean sperm counts are about half of normal but sperm counts vary widely between individuals

decreased testis weight ( J:14233 , J:39106 )

♂ (J:14233)

♂ (J:39106)

delayed vaginal opening ( J:14233 , J:39106 )

• vaginal opening occurs at 7 - 8 weeks of age (J:39106)

abnormal estrous cycle ( J:39106 )

♀ • no normal cycles are detected

decreased litter size ( J:39106 )

• females are usually fertile but have smaller litters when crossed to wild-type mice

infertility ( J:14233 )

• some, but not all, heterozygotes are sterile

female infertility ( J:39106 )

♀ • only 18 of 46 females became pregnant in crosses with heterozygous males previously determined to be fertile

male infertility ( J:39106 )

♂ • 78 of 152 males are sterile and 29 of the remaining 74 are only fertile for a short time

behavior/neurological

hunched posture ( J:39106 )

• sometime mice display a hunched posture without any underlying bony abnormalities of the vertebra or ribs

vision/eye

abnormal eye morphology ( J:39106 )

• eyes are generally half-closed

skeleton

abnormal skeleton morphology ( J:50164 )

• occasionally the cervical-cranial angle is reduced

Wormian bones ( J:50164 )

• a supernumerary element (Wormian bone) is found in the anterior fontanelle

wide metopic suture ( J:50164 )

• wider than normal

wide sagittal suture ( J:50164 )

• wider than normal

increased cranium width ( J:14233 , J:39106 , J:50164 )

• broader in the frontal region (J:39106)

• skull is broader and more bulbous (J:50164)

abnormal anterior fontanelle morphology ( J:50164 )

• a supernumerary element (Wormian bone) is found in the anterior fontanelle

abnormal frontal bone morphology ( J:39106 )

• a small gap between the frontal bones filled with an interfrontal bone is commonly seen

abnormal carpal bone morphology ( J:50164 )

• duplication of carpal bones to the same extent as the increase in digit number

• at E15 the carpus and tarsus consist of 2 rows of indistinct, contiguous elements unlike in wild-type where these elements are discrete and readily identifiable

abnormal tarsal bone morphology ( J:50164 )

• duplication of tarsal bones to the same extent as the increase in digit number

• at E15 the carpus and tarsus consist of 2 rows of indistinct, contiguous elements unlike in wild-type where these elements are discrete and readily identifiable

bowed radius ( J:39106 )

• in some cases the radius is bent

bowed ulna ( J:39106 )

• in some cases the ulna is bent

abnormal fibula morphology ( J:39106 )

• the tibia and fibula fail to fuse

bowed fibula ( J:39106 , J:50164 )

• bowed, probably the result of shortening of the tibia (J:50164)

abnormal tibia morphology ( J:39106 , J:50164 )

• the tibia and fibula fail to fuse (J:39106)

• the tibia has separate proximal and distal sites of chondrogenesis that fuse by E15 but are poorly aligned (J:50164)

• the tibia curves helically around the longitudinal axis and the distal end makes an incomplete, medially situated articulation (J:50164)

• however, the radius and ulna and the rest of the cartilaginous skeleton are normal (J:50164)

bowed tibia ( J:39106 )

decreased length of long bones ( J:14233 , J:39106 )

• long bone are shortened and reduced (J:14233)

• long bones are shortened (J:39106)

short tibia ( J:50164 )

abnormal scapula morphology ( J:39106 , J:50164 )

scapular bone foramen ( J:39106 , J:50164 )

• occasionally a hole is seen in the scapula (J:39106)

• at E17, a hole is sometimes seen in the scapula; however, no hole is seen in mice older then E17 (J:50164)

abnormal thoracic cage shape ( J:50164 )

• occasionally the ribcage is slightly compressed

increased lumbar vertebrae number ( J:39106 )

• occasionally 7 rather than 6 lumber vertebrae are present

endocrine/exocrine glands

decreased testis weight ( J:14233 , J:39106 )

♂ (J:14233)

♂ (J:39106)

embryo

decreased embryo size ( J:50164 )

• seen at E13

broad limb buds ( J:39106 , J:50164 )

• abnormally wide by E11.5 (J:39106)

• by late E10 limbs appear slightly enlarged along the anterior posterior axis; however, at E13 limb length appears normal (J:50164)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
clubfoot		DOID:11836	OMIM:119800	J:39106

Genotype
MGI:3623001

ht3

• Allelic Composition: Dbf/Dbf⁺
• Genetic Background: involves: 101/H * C3H/HeH * M. spretus

craniofacial

craniofacial phenotype ( J:39106 )

N • Background Sensitivity: unlike heterozygotes on a mixed 101/H and C3H/HeH background skull morphology is normal

limbs/digits/tail

limbs/digits/tail phenotype ( J:39106 )

N • Background Sensitivity: unlike heterozygotes on a mixed 101/H and C3H/HeH background tail morphology is normal

polydactyly ( J:39106 )

• similar to heterozygotes on a mixed 101/H and C3H/HeH background

skeleton

abnormal long bone morphology ( J:39106 )

• limb defects are similar to heterozygotes on a mixed 101/H and C3H/HeH background