Phenotypes associated with this allele

• Allele Symbol: Gdf6^tm1Kng
• Allele Name: targeted mutation 1, David M Kingsley
• Allele ID: MGI:2661063
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gdf6^tm1Kng/Gdf6^tm1Kng	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:2661064
cx2	Gdf5^bp-J/Gdf5^bp-J Gdf6^tm1Kng/Gdf6^tm1Kng	involves: 129S1/Sv * 129X1/SvJ * A/J * C57BL/6J	MGI:2661079

Genotype
MGI:2661064

hm1

• Allelic Composition: Gdf6^tm1Kng/Gdf6^tm1Kng
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:83132 )

• fewer than expected homozygotes are detected at 3 to 4 weeks of age

• however, normal Mendelian ratios are observed at E18.5

skeleton

absent coronal suture ( J:83132 )

• at E15.5-E18.5, mutant skulls show no signs of coronal suture formation

abnormal middle ear ossicle morphology ( J:83132 )

• mutant middle ear ossicles display altered shapes

abnormal incus morphology ( J:83132 )

• the mutant incus is reduced in size and displays an altered shape

• gaps between the malleus-incus and incus-stapes joints are observed

abnormal malleus morphology ( J:83132 )

• the mutant malleus is reduced in size and displays an altered shape

• gaps between the malleus-incus joints are observed

abnormal stapes morphology ( J:83132 )

• the mutant stapes is reduced in size and displays an altered shape

• gaps between the incus-stapes joints are observed

• the process at the edges of the stapes where it articulates with the oval window are absent

abnormal stapes annular ligament morphology ( J:83132 )

• the annular ligament which surrounds the base of the stapes and attaches it to the margin of the oval window is significantly thinned or absent

absent stapes annular ligament ( J:83132 )

• in some cases

small middle ear ossicles ( J:83132 )

• mutant middle ear ossicles are reduced in size

small incus ( J:83132 )

small malleus ( J:83132 )

small stapes ( J:83132 )

abnormal carpal bone morphology ( J:83132 )

• some homozygotes display a general disorganization of bones in the carpal region

fused carpal bones ( J:83132 )

• most homozygotes display fusion of 2 or 3 carpal bones in the wrist

abnormal tarsal bone morphology ( J:83132 )

• homozygotes display a dramatically reduced first distal tarsal

fused tarsal bones ( J:83132 )

• homozygotes display fusion of the talus to the central tarsal bone

• fusion of the second and third distal tarsal bones is sometimes observed

abnormal articular cartilage morphology ( J:83132 )

• homozygotes display alterations in the articular surfaces where the malleus meets the incus, the incus meets the stapes, and the stapes meets the oval window

• at E18.5, homozygotes exhibit a significantly reduced rate of cell proliferation along surfaces of the malleus-incus joint and stapes-oval window joints relative to wild-type controls, as shown by BrdU staining

abnormal incudomalleolar joint morphology ( J:83132 )

• gaps between the malleus-incus joints are observed

abnormal incudostapedial joint morphology ( J:83132 )

• gaps between the incus-stapes joints are observed

fused joints ( J:83132 )

• homozygotes exhibit wrist and ankle fusions during early joint development due to failure of the large carpal and tarsal precursors to subdivide into separate skeletal elements at E14.5 and E15.5, respectively

limbs/digits/tail

abnormal carpal bone morphology ( J:83132 )

• some homozygotes display a general disorganization of bones in the carpal region

fused carpal bones ( J:83132 )

• most homozygotes display fusion of 2 or 3 carpal bones in the wrist

abnormal tarsal bone morphology ( J:83132 )

• homozygotes display a dramatically reduced first distal tarsal

fused tarsal bones ( J:83132 )

• homozygotes display fusion of the talus to the central tarsal bone

• fusion of the second and third distal tarsal bones is sometimes observed

craniofacial

absent coronal suture ( J:83132 )

• at E15.5-E18.5, mutant skulls show no signs of coronal suture formation

abnormal middle ear ossicle morphology ( J:83132 )

• mutant middle ear ossicles display altered shapes

abnormal incus morphology ( J:83132 )

• the mutant incus is reduced in size and displays an altered shape

• gaps between the malleus-incus and incus-stapes joints are observed

abnormal malleus morphology ( J:83132 )

• the mutant malleus is reduced in size and displays an altered shape

• gaps between the malleus-incus joints are observed

abnormal stapes morphology ( J:83132 )

• the mutant stapes is reduced in size and displays an altered shape

• gaps between the incus-stapes joints are observed

• the process at the edges of the stapes where it articulates with the oval window are absent

abnormal stapes annular ligament morphology ( J:83132 )

• the annular ligament which surrounds the base of the stapes and attaches it to the margin of the oval window is significantly thinned or absent

absent stapes annular ligament ( J:83132 )

• in some cases

small middle ear ossicles ( J:83132 )

• mutant middle ear ossicles are reduced in size

small incus ( J:83132 )

small malleus ( J:83132 )

small stapes ( J:83132 )

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:83132 )

• mutant middle ear ossicles display altered shapes

abnormal incus morphology ( J:83132 )

• the mutant incus is reduced in size and displays an altered shape

• gaps between the malleus-incus and incus-stapes joints are observed

abnormal malleus morphology ( J:83132 )

• the mutant malleus is reduced in size and displays an altered shape

• gaps between the malleus-incus joints are observed

abnormal stapes morphology ( J:83132 )

• the mutant stapes is reduced in size and displays an altered shape

• gaps between the incus-stapes joints are observed

• the process at the edges of the stapes where it articulates with the oval window are absent

abnormal stapes annular ligament morphology ( J:83132 )

• the annular ligament which surrounds the base of the stapes and attaches it to the margin of the oval window is significantly thinned or absent

absent stapes annular ligament ( J:83132 )

• in some cases

small middle ear ossicles ( J:83132 )

• mutant middle ear ossicles are reduced in size

small incus ( J:83132 )

small malleus ( J:83132 )

small stapes ( J:83132 )

Genotype
MGI:2661079

cx2

• Allelic Composition: Gdf5^bp-J/Gdf5^bp-J; Gdf6^tm1Kng/Gdf6^tm1Kng
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * A/J * C57BL/6J

mortality/aging

premature death ( J:83132 )

• normal mendelian ratios at birth, with less than 5% surviving to adulthood

skeleton

abnormal carpal bone morphology ( J:83132 )

• a severe reduction or absence of carpal bones is observed

abnormal phalanx morphology ( J:83132 )

• a severe reduction of the proximal and middle phalanges of the forelimb is observed

• only remnants of phalanges resembling sesamoid bones or fusions of sesamoid bones and phalanges are noted in the forefeet

absent talus ( J:83132 )

bowed radius ( J:83132 )

• at birth, the radius is bowed and appears to be dislocated from the elbow joint

• however, the radius straightens out by adulthood

short ulna ( J:83132 )

• the ulna is reduced in size, exposing the pisiform underneath

• the ulna appears poorly ossified and shorter than the radius at late stages of embryogenesis and early postnatal stages but becomes fully ossified by adulthood

abnormal metatarsal bone morphology ( J:83132 )

• metatarsal II is split into both a dorsal and a ventral element; both elements are fused to the tarsal bones

scoliosis ( J:83132 )

• in adulthood, 2 of 7 double homozygotes display severe scoliosis with curvatures between 39 and 67 degrees; not observed in newborns

abnormal vertebral articular process morphology ( J:83132 )

• adult double homozygotes display a reduction of Alcian blue-stained cartilage matrix in the intervertebral articular processes between T13 and L2

abnormal vertebral spinous process morphology ( J:83132 )

• adult double homozygotes display a reduction of Alcian blue-stained cartilage matrix in the tip of spinous processes of vertebrae T12 to L3

fused joints ( J:83132 )

• 86% of double homozygotes show fusion of carpal element 4/5 in the forelimb to the proximal end of metacarpal IV; this joint fusion is absent at E18.5 but becomes evident by P6

• 10 of 14 double homozygotes show joint fusions betweeen the metatarsal and proximal phalanx of digit V

• joint fusions between metacarpal and phalange rudiments of multiple digits and between the fibula and calcaneus are also observed

delayed bone ossification ( J:83132 )

• the ulna appears poorly ossified and shorter than the radius at late stages of embryogenesis and early postnatal stages but becomes fully ossified by adulthood

limbs/digits/tail

abnormal carpal bone morphology ( J:83132 )

• a severe reduction or absence of carpal bones is observed

abnormal phalanx morphology ( J:83132 )

• a severe reduction of the proximal and middle phalanges of the forelimb is observed

• only remnants of phalanges resembling sesamoid bones or fusions of sesamoid bones and phalanges are noted in the forefeet

absent talus ( J:83132 )

bowed radius ( J:83132 )

• at birth, the radius is bowed and appears to be dislocated from the elbow joint

• however, the radius straightens out by adulthood

short ulna ( J:83132 )

• the ulna is reduced in size, exposing the pisiform underneath

• the ulna appears poorly ossified and shorter than the radius at late stages of embryogenesis and early postnatal stages but becomes fully ossified by adulthood

abnormal metatarsal bone morphology ( J:83132 )

• metatarsal II is split into both a dorsal and a ventral element; both elements are fused to the tarsal bones

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acromesomelic dysplasia, Grebe type		DOID:0080052	OMIM:200700	J:83132
idiopathic scoliosis		DOID:0060250		J:83132