Phenotypes associated with this allele

• Allele Symbol: Nkx3-2^tm1Bobh
• Allele Name: targeted mutation 1, Robert E Hill
• Allele ID: MGI:1931319
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh	involves: 129P2/OlaHsd * C57BL/6	MGI:2175716
ht2	Nkx3-2^tm1Bobh/Nkx3-2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3608884
cx3	Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh Nkx3-1^tm1Hha/Nkx3-1^tm1Hha	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3608887

Genotype
MGI:2175716

hm1

• Allelic Composition: Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

Skeletal phenotypes of E18.5 Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh fetuses

mortality/aging

perinatal lethality, complete penetrance ( J:57112 )

• homozygotes are present at the expected Mendelian frequencies at E17.5 and E18.5, but appear to die perinatally; no homozygotes are obtained at weaning

neonatal lethality, complete penetrance ( J:79198 , J:93802 )

• no newborn homozygotes survive beyond the first few hours after birth (J:93802)

skeleton

abnormal axial skeleton morphology ( J:57112 )

• homozygotes display a shortened body axis associated with axial skeleton defects in the ventromedial elements of vertebrae that develop around the notochord

abnormal basicranium morphology ( J:57112 )

• homozygotes exhibit abnormalities in bones of the basal skull (i.e. basioccipital and basisphenoid) associated with the notochord

small basioccipital bone ( J:57112 )

• by E18.5, the mutant basioccipital bone appears significantly misshapen and reduced

basioccipital bone hypoplasia ( J:57112 )

• at E14.5 the number of cells at the midline of the mutant basioccipital bone is significantly decreased

small basisphenoid bone ( J:57112 )

• by E18.5, the mutant posterior basisphenoid bone is severely reduced

abnormal middle ear ossicle morphology ( J:88584 )

• at E18.5, homozygotes exhibit a malleus phenotype and lack the predicted malleal/incal fusions due to regulatory changes in genes involved in joint formation

abnormal malleus morphology ( J:88584 )

• although elements of the malleus, such as the processus brevis and the manubrium appear normal, the width, but not the length, of the malleus is significantly decreased

• however, at E18.5, middle ear ossicle development is relatively normal, with the incus and stapes developing as wild-type with respect to both size and articulation

absent gonial bone ( J:88584 )

• at E18.5, all homozygotes lack a gonium, an investing bone that lies on the surface of the malleus

abnormal rib morphology ( J:57112 )

• at E18.5, mutant ribs appear to be tightly spaced and laterally extended but show no other abnormalities such as fusions or disruptions

abnormal vertebrae morphology ( J:57112 )

• at E18.5, mutant vertebrae appear to be more highly compact along the entire vertebral column, with most vertebrae lacking an ossification center in the ventromedial region

• in contrast, mutant sterna remain unaffected, and the size and number of sternabra are comparable to those observed in wild-type mice

small caudal vertebrae ( J:57112 )

• at E18.5, the mutant caudal vertebrae are small and lack the anterior processes

abnormal thoracic vertebrae morphology ( J:57112 )

• at E18.5, homozygotes display a midline clefting in the thoracic vertebrae immediately ventral to the region where the centra of vertebral bodies normally form

• in the thoracic region, vertebral bodies exhibit a narrow ventral bridge linking the lateral vertebral elements of the neural arches; only the centra are missing

abnormal cervical vertebrae morphology ( J:57112 )

• at E18.5, homozygotes exhibit compressed cervical vertebrae relative to wild-type mice

• in the cervical region, all elements at the midline are absent and the neural arches fail to fuse at the midline

abnormal vertebral arch development ( J:57112 )

• in the cervical region, all elements at the midline are absent and the neural arches fail to fuse at the midline

vertebral compression ( J:57112 )

• at E18.5, homozygotes exhibit compressed cervical vertebrae relative to wild-type mice

absent vertebral body ( J:57112 )

• at E18.5, the ventromedial elements of each vertebra, i.e. the vertebral bodies and intervertebral discs, are absent; this phenotype is most prominent in cervical vertebrae

abnormal cartilage morphology ( J:79198 )

• at E17.5, homozygotes show a significant reduction or absence of ventro-medial cartilaginous material in cervical vertebrae

absent intervertebral disk ( J:57112 )

• at E18.5, the ventromedial elements of each vertebra, including the intervertebral discs, are absent

abnormal cartilage development ( J:79198 )

• at E14.5, homozygotes exhibit reduced numbers of chondrogenic cells in the vicinity of the notochord at the cervical level; this effect is less pronounced at the lumbar level

abnormal sclerotome morphology ( J:57112 )

• at E14.5, the cells that compose the lateral elements of the neural arches have condensed in both wild-type and mutant embryos; however, mutants exhibit only a few sclerotomal cells organized around the notochord in the cervical and upper thoracic vertebrae

• in the lumbar region, more sclerotomal cells are apparent at the midline near to the notochord, but appear disorganized

craniofacial

abnormal basicranium morphology ( J:57112 )

• homozygotes exhibit abnormalities in bones of the basal skull (i.e. basioccipital and basisphenoid) associated with the notochord

small basioccipital bone ( J:57112 )

• by E18.5, the mutant basioccipital bone appears significantly misshapen and reduced

basioccipital bone hypoplasia ( J:57112 )

• at E14.5 the number of cells at the midline of the mutant basioccipital bone is significantly decreased

small basisphenoid bone ( J:57112 )

• by E18.5, the mutant posterior basisphenoid bone is severely reduced

abnormal middle ear ossicle morphology ( J:88584 )

• at E18.5, homozygotes exhibit a malleus phenotype and lack the predicted malleal/incal fusions due to regulatory changes in genes involved in joint formation

abnormal malleus morphology ( J:88584 )

• although elements of the malleus, such as the processus brevis and the manubrium appear normal, the width, but not the length, of the malleus is significantly decreased

• however, at E18.5, middle ear ossicle development is relatively normal, with the incus and stapes developing as wild-type with respect to both size and articulation

absent gonial bone ( J:88584 )

• at E18.5, all homozygotes lack a gonium, an investing bone that lies on the surface of the malleus

limbs/digits/tail

small caudal vertebrae ( J:57112 )

• at E18.5, the mutant caudal vertebrae are small and lack the anterior processes

short tail ( J:57112 )

kinked tail ( J:79198 )

thick tail ( J:57112 )

embryo

abnormal left-right axis patterning ( J:93234 )

• homozygotes display regional perturbations of LR asymmetry in the primordial splenopancreatic mesoderm affecting pancreas laterality

abnormal notochord morphology ( J:57112 )

• at E14.5, homozygotes fail to exhibit a repetitive notochordal pattern of swellings in the posterior region, with swollen nodes being either broadened or absent

• in the cervical region, the thin mutant notochord lacks periodic swellings and shows no organized consensation of cells around it

• by E18.5, only a vestigial notochord is present, and the enlarged notochord-derived nucleus pulposus of each intervertebral disc is absent

digestive/alimentary system

abnormal digestive organ placement ( J:93234 )

• homozygotes exhibit regional perturbations of LR asymmetry in the primordial splenopancreatic mesoderm; as a result, the dorsal pancreas remains at the embryonic midline

endocrine/exocrine glands

abnormal pancreas development ( J:93234 )

• at E10 and E10.5, the mutant dorsal pancreatic bud fails to grow laterally and remains positioned along the embryonic midline

• at E13.5, the wild-type dorsal pancreas grows along an axis perpendicular to the duodenum whereas the mutant dorsal pancreas grows along the same axis as the stomach

growth/size/body

decreased body height ( J:57112 )

• at E18.5, mutant fetuses appear slightly shorter and broader than wild-type fetuses

hematopoietic system

absent spleen ( J:57112 )

• at E14.5, homozygotes show no evidence of splenic cells in the splanchnic mesoderm-derived tissue near the stomach

immune system

absent spleen ( J:57112 )

• at E14.5, homozygotes show no evidence of splenic cells in the splanchnic mesoderm-derived tissue near the stomach

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:88584 )

• at E18.5, homozygotes exhibit a malleus phenotype and lack the predicted malleal/incal fusions due to regulatory changes in genes involved in joint formation

abnormal malleus morphology ( J:88584 )

• although elements of the malleus, such as the processus brevis and the manubrium appear normal, the width, but not the length, of the malleus is significantly decreased

• however, at E18.5, middle ear ossicle development is relatively normal, with the incus and stapes developing as wild-type with respect to both size and articulation

absent gonial bone ( J:88584 )

• at E18.5, all homozygotes lack a gonium, an investing bone that lies on the surface of the malleus

abnormal tympanic ring morphology ( J:88584 )

• at E18.5, all homozygotes exhibit a hypoplastic tympanic ring with a portion of the anterior extremity of the ring absent

tympanic ring hypoplasia ( J:88584 )

• at E18.5

Genotype
MGI:3608884

ht2

• Allelic Composition: Nkx3-2^tm1Bobh/Nkx3-2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

limbs/digits/tail

kinked tail ( J:57112 )

• heterozygotes are overtly normal; however, unlike wild-type mice, 46% of heterozygotes exhibit kinked tails

hearing/vestibular/ear

abnormal middle ear morphology ( J:88584 )

abnormal middle ear ossicle morphology ( J:88584 )

• at P2, newborn heterozygotes show signs of fusion between the gonium and the malleus, despite the observed gonium hypoplasia

• moreover, adult heterozygotes show no overt phenotype associated with the earlier gonium hypoplasia, with the malleus, gonium and tympanic forming a continuous skeletal structure

abnormal malleus morphology ( J:88584 )

• although elements of the malleus, such as the processus brevis and the manubrium appear normal, the width (but not the length) of the malleus is significantly decreased

• however, at E18.5, middle ear ossicle development is relatively normal, with the incus and stapes developing as wild-type with respect to both size and articulation

gonial bone hypoplasia ( J:88584 )

• at E18.5, heterozygtes exhibit no overt defects associated with the tympanic ring but do show variable hypoplasia of the gonium, not observed in adulthood

skeleton

abnormal middle ear ossicle morphology ( J:88584 )

• at P2, newborn heterozygotes show signs of fusion between the gonium and the malleus, despite the observed gonium hypoplasia

• moreover, adult heterozygotes show no overt phenotype associated with the earlier gonium hypoplasia, with the malleus, gonium and tympanic forming a continuous skeletal structure

abnormal malleus morphology ( J:88584 )

• although elements of the malleus, such as the processus brevis and the manubrium appear normal, the width (but not the length) of the malleus is significantly decreased

• however, at E18.5, middle ear ossicle development is relatively normal, with the incus and stapes developing as wild-type with respect to both size and articulation

gonial bone hypoplasia ( J:88584 )

• at E18.5, heterozygtes exhibit no overt defects associated with the tympanic ring but do show variable hypoplasia of the gonium, not observed in adulthood

craniofacial

abnormal middle ear ossicle morphology ( J:88584 )

• at P2, newborn heterozygotes show signs of fusion between the gonium and the malleus, despite the observed gonium hypoplasia

• moreover, adult heterozygotes show no overt phenotype associated with the earlier gonium hypoplasia, with the malleus, gonium and tympanic forming a continuous skeletal structure

abnormal malleus morphology ( J:88584 )

• although elements of the malleus, such as the processus brevis and the manubrium appear normal, the width (but not the length) of the malleus is significantly decreased

• however, at E18.5, middle ear ossicle development is relatively normal, with the incus and stapes developing as wild-type with respect to both size and articulation

gonial bone hypoplasia ( J:88584 )

• at E18.5, heterozygtes exhibit no overt defects associated with the tympanic ring but do show variable hypoplasia of the gonium, not observed in adulthood

Genotype
MGI:3608887

cx3

• Allelic Composition: Nkx3-2^tm1Bobh/Nkx3-2^tm1Bobh; Nkx3-1^tm1Hha/Nkx3-1^tm1Hha
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:79198 )

• at E12.5, double homozygotes are present at the expected Mendelian frequency

• however, only ~50% and 15% of the expected number are obtained at E14.5 and E17.5, respectively, with a gradually increasing embryo loss noted between E13.5 and E17.5

• no double homozygotes are recovered alive after E17.5

skeleton

abnormal axial skeleton morphology ( J:79198 )

• at E17.5, the axial skeleton of double homozygotes appears even shorter than that of Bapx1^tm1Bobh homozygotes

abnormal rib morphology ( J:79198 )

• at E17.5, double homozygotes exhibit even more tightly spaced ribs than Bapx1^tm1Bobh homozygotes

abnormal cervical atlas morphology ( J:79198 )

• at E17.5, the double mutant atlas is reduced to only the lateral parts lacking most of the cartilage that gives rise to the vertebral body

abnormal lumbar vertebrae morphology ( J:79198 )

• at E17.5, double mutant lumbar vertebrae completely lack the normal dorsal processes observed as bifurcations in Bapx1^tm1Bobh homozygotes

abnormal vertebrae development ( J:79198 )

• at E17.5, double homozygotes show an enhanced reduction or loss of ventro-medial cartilaginous material in all cervical vertebrae relative to Bapx1^tm1Bobh homozygotes

abnormal vertebral body morphology ( J:79198 )

• at E17.5, double homozygotes lack the central ossification centers in cervical vertebrae, with the atlas being most severely affected; this defect is less obvious in thoracic and lumbar vertebrae

abnormal cartilage development ( J:79198 )

• at E14.5, double homozygotes exhibit a severe reduction in the number of chondrogenic cells around the notochord, with only few scattered cells present at the cervical level but no signs of cartilage formation; at lumbar level, chondrogenic cell numbers are also further reduced relative to Bapx1^tm1Bobh homozygotes

• except for the region of pedicles essentially no cartilage is formed in the vertebral anlagen of double homozygotes

abnormal sclerotome morphology ( J:79198 )

• double homozygotes exhibit exacerbated sclerotomal defects in cervical and lumbar segments relative to Bapx1^tm1Bobh homozygotes

limbs/digits/tail

kinked tail ( J:79198 )

• at E17.5, double homozygotes display severely kinked tails relative to Bapx1^tm1Bobh homozygotes