Phenotypes associated with this allele

• Allele Symbol: Del(6Dlx6-Dlx5)1Tlu
• Allele Name: targeted mutation 1, Thomas Lufkin
• Allele ID: MGI:2388594
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Del(6Dlx6-Dlx5)1Tlu/Del(6Dlx6-Dlx5)1Tlu	involves: Swiss Webster	MGI:3703554
hm2	Del(6Dlx6-Dlx5)1Tlu/Del(6Dlx6-Dlx5)1Tlu	Not Specified	MGI:3703544
ht3	Del(6Dlx6-Dlx5)1Tlu/+	Not Specified	MGI:6209772
cx4	Del(6Dlx6-Dlx5)1Tlu/+ Mef2c^tm1Eno/Mef2c^+	involves: 129S7/SvEvBrd	MGI:6209777

Genotype
MGI:3703554

hm1

• Allelic Composition: Del(6Dlx6-Dlx5)1Tlu/Del(6Dlx6-Dlx5)1Tlu
• Genetic Background: involves: Swiss Webster

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

hearing/vestibular/ear

abnormal outer ear morphology ( J:114449 )

• at E14.5 and E18.5, homozygotes display rudimentary external ear structures

abnormal otic vesicle development ( J:114449 )

• at E9.5, the mutant otocyst is reduced while the otic epithelium is thickened

• at E10.5, the otic vesicle is compressed in both the anterorposterior and dorsoventral planes

• at E10.5, the otic vesicle is abnormally closer to the second branchial arch and farther away from the dorsal neural tube, while the dorsal otic epithelium is relatively closer to the ventral otic epithelium in 95% of cases

• at E11.5, the luminal space of otic vesicles is significantly reduced and appears long and narrow along the mediolateral axis in the dorsoventral plane

• at later stages, all the dorsally-derived otic structures fail to form; only a rudimentary, ventrally-derived cochlea is observed

• at E9.5 and E10.5, BrdU staining indicates decreased cell proliferation in the medial and lateral otic epithelium, while proliferation rates in the periotic mesenchyme remain normal

• at E10.5, TUNEL staining shows increased cell death in both the ventrolateral otic epithelium and periotic mesenchyme

small otic vesicle ( J:114449 )

• mutant otic vesicles appear smaller at E9.5 and developmentally retarded at E10.5

abnormal inner ear morphology ( J:114449 )

• by E11.5, the mutant inner ear resembles an undifferentiated sphere that is half the size of wild-type inner ear

abnormal cochlea morphology ( J:114449 )

• at E16.5, mutant cochlear structures are smaller, rudimentary and completely encapsulated by cartilage

• in addition, mutant cochleas are markedly elongated, vacuolated and rotated caudally

abnormal crista ampullaris neuroepithelium morphology ( J:114449 )

• at E18.5, no ampullae are detected

absent semicircular canals ( J:114449 )

• at E11.5, developing semicircular ducts are completely absent

absent utricle ( J:114449 )

• at E18.5, no utricle is recognized

absent vestibular saccule ( J:114449 )

• at E18.5, no saccule is recognized

absent inner ear vestibule ( J:114449 )

• at E16.5, the entire vestibular portion of the inner ear is presumably absent

absent endolymphatic duct ( J:114449 )

• at E10.5, the outgrowth of the endolymphatic duct fails to form

• at E11.5, the endolymphatic duct is completely absent

abnormal otic capsule morphology ( J:114449 )

• at E16.5 and E18.5, dysmorphic cartilage capsule-like structures adjacent to the basioccipital bone but positioned away form the midline are observed

• at E18.5, cartilage structures that normally compose the vestibular portion of the otic capsule are completely absent

• any remaining cartilage structures are slightly rotated toward the midline and resemble abnormal otic capsules surrounding a presumptive cochlea

small otic capsule ( J:114449 )

• at E16.5 and E18.5, dysmorphic cartilage capsule-like structures are smaller than normal

craniofacial

abnormal outer ear morphology ( J:114449 )

• at E14.5 and E18.5, homozygotes display rudimentary external ear structures

growth/size/body

abnormal outer ear morphology ( J:114449 )

• at E14.5 and E18.5, homozygotes display rudimentary external ear structures

Genotype
MGI:3703544

hm2

• Allelic Composition: Del(6Dlx6-Dlx5)1Tlu/Del(6Dlx6-Dlx5)1Tlu
• Genetic Background: Not Specified

mortality/aging

perinatal lethality, complete penetrance ( J:76480 )

• homozygotes are viable up to E18.5

craniofacial

abnormal craniofacial bone morphology ( J:76480 )

absent Meckel's cartilage ( J:76480 )

• at E14.5, Meckel's cartilage is completely absent

abnormal cranial cartilage development ( J:76480 )

• at E14.5, cartilage giving rise to the cranial floor (basioccipital, basisphenoid, and sphenoid) and frontonasal prominence are present, but show severe patterning defects

• at E14.5, cartilage from the exoccipital and ventral temporal bone primordia extending to the distal nasal capsule appear condensed and fused

• at E16.5, the dysmorphic cranial cartilage structure remains unossified

absent neurocranium ( J:76480 )

• at E16.5, homozygotes show complete absence of calvaria

absent mandible ( J:76480 )

• at E18.5, mandibular structures are dysmorphic

• at E16.5, the mandibular bone is absent

absent maxilla ( J:76480 )

• at E18.5, maxillary structures are dysmorphic

• at E16.5, the maxillary bone is absent

abnormal nasal bone morphology ( J:76480 )

• at E18.5, nasal structures are dysmorphic

abnormal nasal capsule morphology ( J:76480 )

• at E14.5, the outgrowth of the dysmorphic nasal prominence is curved caudally

abnormal pharyngeal arch morphology ( J:76480 )

• at E11.5, homozygotes display dysmorphic branchial arch derivatives

nasal cartilage hypoplasia ( J:139700 )

• the nasal cartilage is hypoplastic

abnormal nasal cavity morphology ( J:76480 )

• at E14.5, homozygotes show severe clefting of the entire nasal cavity

abnormal outer ear cartilage morphology ( J:76480 )

• at E14.5, external ear cartilage is absent

skeleton

abnormal nasal capsule morphology ( J:76480 )

• at E14.5, the outgrowth of the dysmorphic nasal prominence is curved caudally

nasal cartilage hypoplasia ( J:139700 )

• the nasal cartilage is hypoplastic

abnormal outer ear cartilage morphology ( J:76480 )

• at E14.5, external ear cartilage is absent

abnormal limb bone morphology ( J:76480 )

• at E14.5, all combinations of the central digits are absent, with missing cartilage including phalanges, metatarsals, and tarsals

abnormal axial skeleton morphology ( J:76480 )

• at E16.5, the axial skeleton, including vertebral bodies shows little or no ossification

abnormal craniofacial bone morphology ( J:76480 )

absent Meckel's cartilage ( J:76480 )

• at E14.5, Meckel's cartilage is completely absent

abnormal cranial cartilage development ( J:76480 )

• at E14.5, cartilage giving rise to the cranial floor (basioccipital, basisphenoid, and sphenoid) and frontonasal prominence are present, but show severe patterning defects

• at E14.5, cartilage from the exoccipital and ventral temporal bone primordia extending to the distal nasal capsule appear condensed and fused

• at E16.5, the dysmorphic cranial cartilage structure remains unossified

absent neurocranium ( J:76480 )

• at E16.5, homozygotes show complete absence of calvaria

absent mandible ( J:76480 )

• at E18.5, mandibular structures are dysmorphic

• at E16.5, the mandibular bone is absent

absent maxilla ( J:76480 )

• at E18.5, maxillary structures are dysmorphic

• at E16.5, the maxillary bone is absent

abnormal nasal bone morphology ( J:76480 )

• at E18.5, nasal structures are dysmorphic

abnormal rib morphology ( J:76480 )

• at E16.5 and E18.5, the ribs are malformed, esp. in the region proximal to the vertebral column

decreased osteoblast cell number ( J:76480 )

• at E16.5, accumulation of mature osteoblasts is severely retarded or absent in mutant scapulas

absent cartilage ( J:76480 )

• at E14.5, Alcian blue staining indicates absence of cartilage in frontonasal, supraoccipital, and rostral temporal areas, nasal prominence and central digits

• at E14.5, external ear cartilage is absent

delayed bone ossification ( J:76480 )

• at E16.5, homozygotes display either delayed or no ossification in the forelimbs

• at E16.5, the dysmorphic cranial cartilage structure remains unossified

• at E16.5, the axial skeleton, including vertebral bodies shows little or no ossification

• delay in ossification becomes less severe in the axial and appendicular skeleton by E18.5

delayed endochondral bone ossification ( J:76480 )

• at E16.5, endochondral ossification is either absent or delayed in all bones of the appendicular and axial skeleton

• at E18.5, transition from a cartilaginous to ossified skeleton remains severely retarded

limbs/digits/tail

thin apical ectodermal ridge ( J:76480 )

• at E11.5, the medial portion at the hindlimb AER is thinner and the distal edge of the hindlimb is flattened

• at E10.5 and E11.5, BrdU incorporation indicates decreased cellular proliferation in the medial AER with subsequent loss of limb structures (medial digits), while proliferation in the underlying mesenchyme is unaffected

abnormal digit morphology ( J:76480 )

• at E16.5 and E18.5, forelimb and hindlimb digits are absent and/or fused

• at E14.5, the central digit is most commonly lost

ectrodactyly ( J:76480 )

• by E14.5, one to three of the central hindlimb digits are absent in all homozygotes

syndactyly ( J:76480 )

• at E14.5, the central hindlimb digit is absent while the remaining adjacent digits tend to be either misshapen or fused at phalanges or metatarsals

• similar defects are occasionally observed in the forelimbs

abnormal forelimb morphology ( J:76480 )

• at E16.5, forelimbs display either delayed or no ossification

• at E18.5, the ratio of forelimb ossification to cartilage remains retarded

• at E18.5, forelimbs display clefting due to missing and/or fused digits

abnormal hindlimb morphology ( J:76480 )

• at E18.5, homozygotes display split hindlimbs with complete penetrance

• at E11.5, the distal edge of hindlimbs is flattened

• at E16.5, hindlimbs display clefting due to missing and/or fused digits

abnormal limb bone morphology ( J:76480 )

• at E14.5, all combinations of the central digits are absent, with missing cartilage including phalanges, metatarsals, and tarsals

kinked tail ( J:76480 )

• at E11.5, mutant embryos exhibit kinked tail vertebrae

nervous system

open neural tube ( J:76480 )

• at E9.5, the anterior neuropore fails to close

exencephaly ( J:76480 )

• at E18.5, homozygotes display exencephaly, leading to cerebral trauma during fetal delivery and massive postnatal blood loss

hearing/vestibular/ear

abnormal outer ear cartilage morphology ( J:76480 )

• at E14.5, external ear cartilage is absent

abnormal inner ear morphology ( J:76480 )

• at E11.5, homozygotes show absence of inner ear structures

abnormal otic capsule morphology ( J:76480 , J:139700 )

• at E14.5, the inner ear capsule and middle ear cartilages are fused and highly dysmorphic (J:76480)

• mice are dorsally deficient in the otic capsule (J:139700)

abnormal middle ear morphology ( J:76480 )

• at E14.5, the inner ear capsule and middle ear cartilages are fused and highly dysmorphic

vision/eye

abnormal eye development ( J:76480 )

• at E11.5, homozygotes show absence of developing eyes

microphthalmia ( J:76480 )

• at E18.5, homozygotes display reduced eye size

respiratory system

abnormal nasal bone morphology ( J:76480 )

• at E18.5, nasal structures are dysmorphic

abnormal nasal capsule morphology ( J:76480 )

• at E14.5, the outgrowth of the dysmorphic nasal prominence is curved caudally

nasal cartilage hypoplasia ( J:139700 )

• the nasal cartilage is hypoplastic

abnormal nasal cavity morphology ( J:76480 )

• at E14.5, homozygotes show severe clefting of the entire nasal cavity

growth/size/body

abnormal nasal bone morphology ( J:76480 )

• at E18.5, nasal structures are dysmorphic

abnormal nasal capsule morphology ( J:76480 )

• at E14.5, the outgrowth of the dysmorphic nasal prominence is curved caudally

nasal cartilage hypoplasia ( J:139700 )

• the nasal cartilage is hypoplastic

abnormal nasal cavity morphology ( J:76480 )

• at E14.5, homozygotes show severe clefting of the entire nasal cavity

abnormal outer ear cartilage morphology ( J:76480 )

• at E14.5, external ear cartilage is absent

decreased fetal size ( J:76480 )

• at E18.5, homozygotes display an overall reduced size relative to wild-type fetuses

embryo

abnormal pharyngeal arch morphology ( J:76480 )

• at E11.5, homozygotes display dysmorphic branchial arch derivatives

thin apical ectodermal ridge ( J:76480 )

• at E11.5, the medial portion at the hindlimb AER is thinner and the distal edge of the hindlimb is flattened

• at E10.5 and E11.5, BrdU incorporation indicates decreased cellular proliferation in the medial AER with subsequent loss of limb structures (medial digits), while proliferation in the underlying mesenchyme is unaffected

open neural tube ( J:76480 )

• at E9.5, the anterior neuropore fails to close

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
split hand-foot malformation 1		DOID:0090021	OMIM:183600	J:76480

Genotype
MGI:6209772

ht3

• Allelic Composition: Del(6Dlx6-Dlx5)1Tlu/+
• Genetic Background: Not Specified

mortality/aging

mortality/aging ( J:122483 )

N • heterozygotes appear normal at birth and generally survive to weaning; only 2 of 13 mice born are scored as dead or clearly cyanotic and dying, indicating that neonatal viability is not significantly affected relative to wild-type controls

Genotype
MGI:6209777

cx4

• Allelic Composition: Del(6Dlx6-Dlx5)1Tlu/+; Mef2c^tm1Eno/Mef2c⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

neonatal lethality, complete penetrance ( J:122483 )

• all (9 of 9) double heterozygous mice are clearly cyanotic at birth and die on postnatal day 0 (P0)

craniofacial

abnormal palate development ( J:122483 )

• at P0, mice exhibit a small, misshapen, and incomplete palate

glossoptosis ( J:122483 )

• at P0, mice show an improper position of the tongue at the rear of the oral cavity

homeostasis/metabolism

cyanosis ( J:122483 )

• all mice are clearly cyanotic at birth

growth/size/body

abnormal palate development ( J:122483 )

• at P0, mice exhibit a small, misshapen, and incomplete palate

glossoptosis ( J:122483 )

• at P0, mice show an improper position of the tongue at the rear of the oral cavity

digestive/alimentary system

abnormal palate development ( J:122483 )

• at P0, mice exhibit a small, misshapen, and incomplete palate

glossoptosis ( J:122483 )

• at P0, mice show an improper position of the tongue at the rear of the oral cavity