Phenotypes associated with this allele

• Allele Symbol: Chuk^tm1Mka
• Allele Name: targeted mutation 1, Michael Karin
• Allele ID: MGI:1857768
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chuk^tm1Mka/Chuk^tm1Mka	B6.129-Chuk^tm1Mka	MGI:3841114
hm2	Chuk^tm1Mka/Chuk^tm1Mka	involves: 129S1/Sv * 129X1/SvJ	MGI:5426894
hm3	Chuk^tm1Mka/Chuk^tm1Mka	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA	MGI:3609030
cx4	Chuk^tm1Mka/Chuk^+ Sfn^Er/Sfn^Er	involves: 129S1/Sv * 129X1/SvJ	MGI:5426900
cx5	Chuk^tm1Mka/Chuk^+ Irf6^tm1Mjd/Irf6^tm1Mjd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5426904
cx6	Chuk^tm1Mka/Chuk^tm1Mka Irf6^tm1Mjd/Irf6^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5426902

Genotype
MGI:3841114

hm1

• Allelic Composition: Chuk^tm1Mka/Chuk^tm1Mka
• Genetic Background: B6.129-Chuk^tm1Mka

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

immune system

abnormal B cell physiology ( J:113556 )

• there is about a third reduction in the number of B cells that survive 36 hours of in vitro culturing compared to controls

• addition of Tnfsf13b (BAFF) to the culture does not elevate survival

hematopoietic system

abnormal B cell physiology ( J:113556 )

• there is about a third reduction in the number of B cells that survive 36 hours of in vitro culturing compared to controls

• addition of Tnfsf13b (BAFF) to the culture does not elevate survival

Genotype
MGI:5426894

hm2

• Allelic Composition: Chuk^tm1Mka/Chuk^tm1Mka
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

craniofacial

abnormal craniofacial development ( J:184926 )

• at E13.5, surface epithelium exhibits cobblestone-like cells unlike in wild-type mice

• however, cobblestone-like cells are absent at E18.5

Genotype
MGI:3609030

hm3

• Allelic Composition: Chuk^tm1Mka/Chuk^tm1Mka
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA

mortality/aging

neonatal lethality, complete penetrance ( J:54316 )

• homozygotes are born alive but die within 30 min after birth, probably due to cardiovascular malfunction

skeleton

abnormal cranium morphology ( J:54316 )

• at E18, mutant skulls appear shorter and maldeveloped relative to wild-type skulls

decreased cranium height ( J:54316 )

small cranium ( J:54316 )

wide frontal bone ( J:54316 )

• at birth, the mutant frontal bone is wider than that of wild-type mice

small interparietal bone ( J:54316 )

• newborn homozygotes exhibit a reduced interparietal bone

small parietal bone ( J:54316 )

• newborn homozygotes exhibit a reduced parietal bone

abnormal presphenoid bone morphology ( J:54316 )

• newborn homozygotes lack a portion of the presphenoid bone; in contrast, the basioccipital and basisphenoid bones appear grossly normal

abnormal incisor morphology ( J:90053 )

• newborn homozygotes exhibit shorter maxillary and mandibular incisors with enlarged crowns; their anterior extents are enlarged and already exposed to the oral cavity at birth

• at E13, the mutant incisor tooth germ epithelium evaginates into the developing oral cavity rather than invaginating into underlying mesenchyme

abnormal molar cusp morphology ( J:90053 )

• newborn homozygotes have molars with rounded and shallow cusps

abnormal enamel knot morphology ( J:90053 )

• at E14.5-E15.5, when the primary enamel knot is histologically evident, mutant molar tooth germs exhibit a slight reduction in the size of enamel knots

short mandible ( J:54316 )

small vomer bone ( J:54316 )

• newborn homozygotes exhibit a significantly reduced vomer relative to wild-type newborns

abnormal zygomatic bone morphology ( J:54316 )

• newborn homozygotes exhibit a reduced space between the pterygoid and jugal bones

abnormal nasal capsule morphology ( J:54316 )

• newborn homozygotes exhibit a reduced nasal capsule

abnormal phalanx morphology ( J:54316 )

• at birth, mutant hindpaws are completely devoid of phalanges; mutant forepaws display fusion of the first phalanges of digits III and IV and loss of the second and third phalanges

split xiphoid process ( J:54316 )

• the mutant xiphoid process fails to fuse and appears bifurcated

short sternum ( J:54316 )

• at E16 and at birth, homozygotes display a shorter sternum that fails to fuse

small thoracic cage ( J:54316 )

• at E18, homozygotes exhibit smaller rib cages than wild-type mice

cervical vertebral fusion ( J:54316 )

• at E18, many of the mutant cervical vertebrae appear fused

abnormal sacral vertebrae morphology ( J:54316 )

sacral vertebral fusion ( J:54316 )

• at E18, many of the mutant sacral vertebrae appear fused

small sacral vertebrae ( J:54316 )

• at E18, many of the mutant sacral vertebrae appear small

short vertebral column ( J:54316 )

• at E18, homozygotes exhibit smaller vertebral columns than wild-type mice

abnormal chondrocyte differentiation ( J:54316 )

• newborn homozygotes exhibit defects in chondrocyte differentiation, with reduced concentration of collagen fibers and uncondensed nuclei in hypertrophied chondrocytes

decreased bone mineralization ( J:54316 )

• mutant digits are only partially mineralized

delayed bone ossification ( J:54316 )

• at birth, mutant sterna display delayed ossification

craniofacial

abnormal cranium morphology ( J:54316 )

• at E18, mutant skulls appear shorter and maldeveloped relative to wild-type skulls

decreased cranium height ( J:54316 )

small cranium ( J:54316 )

wide frontal bone ( J:54316 )

• at birth, the mutant frontal bone is wider than that of wild-type mice

small interparietal bone ( J:54316 )

• newborn homozygotes exhibit a reduced interparietal bone

small parietal bone ( J:54316 )

• newborn homozygotes exhibit a reduced parietal bone

abnormal presphenoid bone morphology ( J:54316 )

• newborn homozygotes lack a portion of the presphenoid bone; in contrast, the basioccipital and basisphenoid bones appear grossly normal

abnormal incisor morphology ( J:90053 )

• newborn homozygotes exhibit shorter maxillary and mandibular incisors with enlarged crowns; their anterior extents are enlarged and already exposed to the oral cavity at birth

• at E13, the mutant incisor tooth germ epithelium evaginates into the developing oral cavity rather than invaginating into underlying mesenchyme

abnormal molar cusp morphology ( J:90053 )

• newborn homozygotes have molars with rounded and shallow cusps

abnormal enamel knot morphology ( J:90053 )

• at E14.5-E15.5, when the primary enamel knot is histologically evident, mutant molar tooth germs exhibit a slight reduction in the size of enamel knots

short mandible ( J:54316 )

small vomer bone ( J:54316 )

• newborn homozygotes exhibit a significantly reduced vomer relative to wild-type newborns

abnormal zygomatic bone morphology ( J:54316 )

• newborn homozygotes exhibit a reduced space between the pterygoid and jugal bones

abnormal nasal capsule morphology ( J:54316 )

• newborn homozygotes exhibit a reduced nasal capsule

small nasal septum ( J:54316 )

• newborn homozygotes exhibit a reduced nasal septum

short snout ( J:54316 )

shortened head ( J:54316 )

anotia ( J:54316 )

• at E18, homozygotes lack external ears

limbs/digits/tail

abnormal limb morphology ( J:54316 )

• at E18, homozygotes display rudimentary protrusions instead of normal external limbs; however, limb bones are only mildly truncated and of a relatively normal shape

abnormal apical ectodermal ridge morphology ( J:54316 )

• defective epidermal differentiation may impair production of morphogens by epidermal thickenings, such as the AER, contributing to aberrant limb patterning

abnormal phalanx morphology ( J:54316 )

• at birth, mutant hindpaws are completely devoid of phalanges; mutant forepaws display fusion of the first phalanges of digits III and IV and loss of the second and third phalanges

brachydactyly ( J:54316 )

• at birth, mutant digits are half the length of wild-type digits

syndactyly ( J:54316 )

• at E14.5 and E16, mutant fore- and hindlimbs lack digit separation

interdigital webbing ( J:54316 )

• at E13, mutant forepaws fail to form distinct digits and display a webbed morphology as a result of reduced apoptosis in the interdigital region

short forelimb ( J:54316 )

• at E16, mutant forelimbs (but not hindlimbs) are shorter than wild-type forelimbs

• however, no significant forelimb truncation is noted at E14.5

abnormal tail morphology ( J:54316 )

• at E18, homozygotes exhibit malformed tails

embryo

abnormal placenta vasculature ( J:54316 )

• at birth, mutant placentae exhibit severe congestion of expanded blood vessels and sinuses on the maternal surface

abnormal apical ectodermal ridge morphology ( J:54316 )

• defective epidermal differentiation may impair production of morphogens by epidermal thickenings, such as the AER, contributing to aberrant limb patterning

hearing/vestibular/ear

anotia ( J:54316 )

• at E18, homozygotes lack external ears

digestive/alimentary system

esophageal atresia ( J:54316 )

• at E17, homozotes exhibit closure of the esophagus resulting from keratinocyte abundance

respiratory system

abnormal nasal capsule morphology ( J:54316 )

• newborn homozygotes exhibit a reduced nasal capsule

small nasal septum ( J:54316 )

• newborn homozygotes exhibit a reduced nasal septum

growth/size/body

abnormal incisor morphology ( J:90053 )

• newborn homozygotes exhibit shorter maxillary and mandibular incisors with enlarged crowns; their anterior extents are enlarged and already exposed to the oral cavity at birth

• at E13, the mutant incisor tooth germ epithelium evaginates into the developing oral cavity rather than invaginating into underlying mesenchyme

abnormal molar cusp morphology ( J:90053 )

• newborn homozygotes have molars with rounded and shallow cusps

abnormal enamel knot morphology ( J:90053 )

• at E14.5-E15.5, when the primary enamel knot is histologically evident, mutant molar tooth germs exhibit a slight reduction in the size of enamel knots

abnormal nasal capsule morphology ( J:54316 )

• newborn homozygotes exhibit a reduced nasal capsule

small nasal septum ( J:54316 )

• newborn homozygotes exhibit a reduced nasal septum

short snout ( J:54316 )

shortened head ( J:54316 )

anotia ( J:54316 )

• at E18, homozygotes lack external ears

decreased birth body size ( J:54316 )

• at birth, homozygotes are smaller than wild-type newborns and resemble E18 mutant fetuses

• notably, most major internal organs (including the heart, lungs, liver, kidneys, spleen, brain, and spinal cord), appear grossly normal

omphalocele ( J:54316 )

• at E18, homozygotes exhibit an omphalocele where the gastrointestinal tract protrudes into the umbilical cord to form an external sac

vision/eye

abnormal anterior eye segment morphology ( J:65553 )

• newborn homozygotes show impaired development and differentiation of the cornea and conjunctiva, consistent with impaired expression of K12 (a marker for differentiated corneal epithelial cells) and K4 (a marker for conjunctival epithelial cells)

abnormal conjunctiva morphology ( J:65553 )

• at birth, the mutant conjunctiva is composed of cells with rounded nuclei instead of flattened differentiated cells, and continues to express high levels of K5, indicating nondifferentiation of basal cells

• absence of nuclear p50 staining and defective differentiation of the mutant conjunctiva suggest that the nuclear translocation of NF-kappaB is critical for the differentiation of the developing conjunctival epithelium

disorganized cornea epithelium ( J:65553 )

• at birth, the mutant corneal epithelial layer is poorly organized and consists of several layers of more rounded cells instead of two layers of flat cells of ectodermal origin

abnormal cornea stroma morphology ( J:65553 )

• at birth, the mutant corneal stroma is poorly organized and composed of several layers of rounded cells instead of several ordered layers of mesenchymal cells

abnormal eyelid morphology ( J:65553 )

• at birth, mutant eyes exhibit a multicellular layer of immature ectodermal cells that covers the cornea and fuses the cornea to the eyelid, preventing the sliding of upper and lower eyelids on the corneal surface

eyelids open at birth ( J:65553 )

• although the eyes of newborn homozygotes appear wide open in the dissection microscope, they are in fact closed with underdeveloped eyelids

cellular

cellular phenotype ( J:54316 )

N • in culture, MEFs obtained from at E13 homozygotes exhibit normal IKK activation and IkappaBalpha degradation in response to proinflammatory stimuli

abnormal keratinocyte differentiation ( J:54316 )

• at E18, homozygotes show a complete block of keratinocyte differentiation, resulting in absence of a stratified, well-differentiated epidermis

integument

abnormal vibrissa follicle morphology ( J:90053 )

• at E14, mutant whisker follicles display an abnormal epithelium evagination, similar to that observed in mutant incisor tooth germ epithelium

abnormal skin morphology ( J:54316 )

abnormal keratinocyte differentiation ( J:54316 )

• at E18, homozygotes show a complete block of keratinocyte differentiation, resulting in absence of a stratified, well-differentiated epidermis

absent epidermis stratum corneum ( J:54316 )

absent epidermis stratum granulosum ( J:54316 )

• at E18, homozygotes exhibit absence of the stratum granulosum

abnormal epidermis stratum spinosum morphology ( J:54316 )

• at E18, homozygotes exhibit hyperplasia of the stratum spinosum of the epidermis

abnormal epidermis suprabasal layer morphology ( J:54316 )

• at E18, homozygotes exhibit increased thickness of the suprabasal layer as a result of increased cell proliferation

epidermal hyperplasia ( J:54316 )

thick epidermis ( J:54316 )

tight skin ( J:54316 )

• at E16 and E18, homozygotes display a taut, smooth skin lacking the characteristic folds and wrinkles of wild-type skin

thick skin ( J:54316 )

• mutant hindlimbs and tail are surrounded by a thick layer of skin that is abnormally fused to the skin cover of the body

abnormal skin physiology ( J:54316 )

• at E17, the mutant epidermis displays increased adhesiveness, with the highest concentration of proteoglycans in the area where the skin that normally surrounds the limb is fused to the skin surrounding the body

cardiovascular system

abnormal placenta vasculature ( J:54316 )

• at birth, mutant placentae exhibit severe congestion of expanded blood vessels and sinuses on the maternal surface

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fetal encasement syndrome		DOID:0060647	OMIM:613630	J:195185

Genotype
MGI:5426900

cx4

• Allelic Composition: Chuk^tm1Mka/Chuk⁺; Sfn^Er/Sfn^Er
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

craniofacial

craniofacial phenotype ( J:184926 )

N • mice exhibit normal teeth and molar tooth germ

Genotype
MGI:5426904

cx5

• Allelic Composition: Chuk^tm1Mka/Chuk⁺; Irf6^tm1Mjd/Irf6^tm1Mjd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

craniofacial

abnormal incisor morphology ( J:184926 )

• the evaginating incisor phenotype is neither attenuated or worsened compared with Irf6^tm1Mjd homozygotes

growth/size/body

abnormal incisor morphology ( J:184926 )

• the evaginating incisor phenotype is neither attenuated or worsened compared with Irf6^tm1Mjd homozygotes

skeleton

abnormal incisor morphology ( J:184926 )

• the evaginating incisor phenotype is neither attenuated or worsened compared with Irf6^tm1Mjd homozygotes

Genotype
MGI:5426902

cx6

• Allelic Composition: Chuk^tm1Mka/Chuk^tm1Mka; Irf6^tm1Mjd/Irf6⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

craniofacial

abnormal incisor morphology ( J:184926 )

• the evaginating incisor phenotype is neither attenuated or worsened compared with Chuk^tm1Mka homozygotes

growth/size/body

abnormal incisor morphology ( J:184926 )

• the evaginating incisor phenotype is neither attenuated or worsened compared with Chuk^tm1Mka homozygotes

skeleton

abnormal incisor morphology ( J:184926 )

• the evaginating incisor phenotype is neither attenuated or worsened compared with Chuk^tm1Mka homozygotes