Mouse Genome Informatics
hm
    Dlx5/Dlx6tm1Levi/Dlx5/Dlx6tm1Levi
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes are recovered up to E18 but die shortly after birth

limbs/digits/tail
• at E14.5 and E18, mutant hindlimbs display shortening or absence of central digits, often associated with deformation, syndactyly, and a severe medial cleft
• at E14.5 and E18, mutant hindlimbs show a distal defect of the 3rd and 4th phalanxes
• at E14.5 and E18, mutant hindlimbs display shortening of central digits
• newborn homozygotes exhibit bilateral ectrodactyly of the posterior limbs (J:77244)
• mice exhibit ectrodactyly of the hindlimbs that is not observed in heterozygous mice or Dlx5 null mice (J:135784)
• however, forelimbs hands are normal (J:135784)
• at E14.5 and E18, mutant hindlimbs with missing digits are often associated with syndactyly of the remaining digits
• at E11.5-E12.5, the central part of the mutant hindlimb palette appears flattened or indented, with a high degree of variability between left and right hindlimbs
• in contrast, no forelimb defects are observed
• at E14.5 and E18, mutant hindlimbs show a distal defect of the 3rd and 4th metatarsals
• in contrast, no malformations of tarsal bones or other proximal elements are observed

craniofacial
• at E14.5 and at birth, homozygotes show fusions between the hyoid bone and the pterygoid processes of the sphenoid bone and the superior horns of the thyroid
• most affected craniofacial structures are neural-crest-derived
• malformation of cephalic or presomitic mesoderm derived cranial structures is probably secondary to failure of neural tube closure or the primary skull defects in the viscerocranium
• at birth, the anterior skull base is severely malformed
• at birth, the skull plates are virtually absent
• at birth, the basisphenoid is distorted and bent to allow articulation of the pterygoid process with the transformed lower jaw
• at birth, the alisphenoids are duplicated
• at birth, the presphenoid is severely reduced
• at E12.5 and at birth, both upper and lower jaws are severely affected and appear as mirror-images of each other
• strikingly, whisker pads with vibrissal follicles are observed on both the upper and the lower jaws
• structures resembling palatine rugae (i.e. a series of ridges associated with the inner surfaces of palatal shelves) are found on the inner surface of both upper and lower jaws
• homozygotes show a homeotic transformation of the lower jaw into an upper jaw, resulting in snout symmetry
• at E14.5, the mandible becomes unrecognizable and is transformed into a structure indistinguishable from the deformed maxillary bone complex
• the tranformed lower jaw appears to articulate with structures resembling distorted, duplicated pterygoid processes, rather than with the squamosal bone
• at E14.5, the maxillary group of bones is structurally identifiable but severely distorted
• at birth, the incus, malleus and stapes are all affected
• newborn homozygotes show severe craniofacial defects associated with a homeotic transformation of the mandibular arch
• at E14.5, Meckel's cartilage is almost completely absent, though a small rudiment is found in the distalmost part of the lower jaw in some embryos
• transformation of the mandibular process into a maxillary process is first evident at ~E10.5-E11.0, when mandibular processes fail to fuse and are slightly increased in size
• at E14.5, most-derivatives of the first, second, and third branchial arch are distorted and fused while the ala temporalis is duplicated
• branchial arch abnormalities are first evident at E10.5-E11.0
• newborn homozygotes display an apparent homeotic transformation of the entire mandibular (first pharyngeal) arch
• newborn homozygotes display an abnormally symmetrical mouth
• at E12.5 and at birth, homozygotes exhibit gain-of-symmetry of the snout both along the right-left and antero-posterior planes

skeleton
• at E14.5 and at birth, homozygotes show fusions between the hyoid bone and the pterygoid processes of the sphenoid bone and the superior horns of the thyroid
• most affected craniofacial structures are neural-crest-derived
• malformation of cephalic or presomitic mesoderm derived cranial structures is probably secondary to failure of neural tube closure or the primary skull defects in the viscerocranium
• at birth, the anterior skull base is severely malformed
• at birth, the skull plates are virtually absent
• at birth, the basisphenoid is distorted and bent to allow articulation of the pterygoid process with the transformed lower jaw
• at birth, the alisphenoids are duplicated
• at birth, the presphenoid is severely reduced
• at E12.5 and at birth, both upper and lower jaws are severely affected and appear as mirror-images of each other
• strikingly, whisker pads with vibrissal follicles are observed on both the upper and the lower jaws
• structures resembling palatine rugae (i.e. a series of ridges associated with the inner surfaces of palatal shelves) are found on the inner surface of both upper and lower jaws
• homozygotes show a homeotic transformation of the lower jaw into an upper jaw, resulting in snout symmetry
• at E14.5, the mandible becomes unrecognizable and is transformed into a structure indistinguishable from the deformed maxillary bone complex
• the tranformed lower jaw appears to articulate with structures resembling distorted, duplicated pterygoid processes, rather than with the squamosal bone
• at E14.5, the maxillary group of bones is structurally identifiable but severely distorted
• at birth, the incus, malleus and stapes are all affected
• at E14.5, Meckel's cartilage is almost completely absent, though a small rudiment is found in the distalmost part of the lower jaw in some embryos
• at E14.5 and E18, mutant hindlimbs show a distal defect of the 3rd and 4th phalanxes
• at E14.5 and E18, mutant hindlimbs show a distal defect of the 3rd and 4th metatarsals
• in contrast, no malformations of tarsal bones or other proximal elements are observed
• the stylohyoid ligament is often chondrified

embryogenesis
• at E14.5, most-derivatives of the first, second, and third branchial arch are distorted and fused while the ala temporalis is duplicated
• branchial arch abnormalities are first evident at E10.5-E11.0
• newborn homozygotes display an apparent homeotic transformation of the entire mandibular (first pharyngeal) arch

nervous system
• exencephaly is clearly evident at E9.5

hearing/vestibular/ear
• at birth, the incus, malleus and stapes are all affected

digestive/alimentary system

respiratory system

integument
• strikingly, at E12.5, whisker pads with vibrissal follicles are observed on both the upper and the lower jaws

growth/size/body
• newborn homozygotes display an abnormally symmetrical mouth
• at E12.5 and at birth, homozygotes exhibit gain-of-symmetry of the snout both along the right-left and antero-posterior planes

Mouse Models of Human Disease
OMIM IDRef(s)
Split-Hand/Foot Malformation 1; SHFM1 183600 J:77244