Phenotypes associated with this allele

• Allele Symbol: Celsr1^Crsh
• Allele Name: crash
• Allele ID: MGI:2668337
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Celsr1^Crsh/Celsr1^Crsh	C3H.Cg-Celsr1^Crsh	MGI:5661738
hm2	Celsr1^Crsh/Celsr1^Crsh	either: (involves: 101/H * C3H/HeH) or (involves: 101/H * BALB/c * C3H/HeH)	MGI:4948448
hm3	Celsr1^Crsh/Celsr1^Crsh	involves: 101/H * BALB/c * C3H/HeH	MGI:2668349
ht4	Celsr1^Crsh/Celsr1^+	C3H.Cg-Celsr1^Crsh	MGI:5661735
ht5	Celsr1^Crsh/Celsr1^+	involves: 101/H * BALB/c * C3H/HeH	MGI:2668352
ht6	Celsr1^Crsh/Celsr1^Scy	involves: 101/H * BALB/c * C3H/He * C3H/HeH	MGI:3690972
cx7	Celsr1^Crsh/Celsr1^+ Scrib^Crc/Scrib^+	C3H.Cg-Scrib^Crc Celsr1^Crsh	MGI:5661818
cx8	Celsr1^Crsh/Celsr1^+ Vangl2^Lp/Vangl2^+	C3H.Cg-Vangl2^Lp Celsr1^Crsh	MGI:5661740
cx9	Celsr1^Crsh/Celsr1^+ Scrib^Crc/Scrib^+ Vangl2^Lp/Vangl2^+	C3H.Cg-Vangl2^Lp Scrib^Crc Celsr1^Crsh	MGI:5661822
cx10	Celsr1^Crsh/Celsr1^+ Ptk7^chz/Ptk7^+	involves: 101/H * BALB/c * BALB/cAnN * C3H/HeH	MGI:4830334
cx11	Celsr1^Crsh/Celsr1^+ Scrib^Crc/Scrib^+	involves: 101/H * BALB/c * C3H/HeH * C57BL/6 * NMRI	MGI:5661724
cx12	Celsr1^Crsh/Celsr1^+ Vangl2^Lp/Vangl2^+	involves: 101/H * BALB/c * C3H/HeH * CBA * LPT/Le	MGI:5661720

Genotype
MGI:5661738

hm1

• Allelic Composition: Celsr1^Crsh/Celsr1^Crsh
• Genetic Background: C3H.Cg-Celsr1^Crsh

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

embryo

abnormal neural plate morphology ( J:216413 )

• broader neural plate with enlargement of the ventral midline and notochord is seen around the time of neural tube closure initiation

open neural tube ( J:216413 )

• embryos fail to initiate neural tube closure, with 100% open neural tubes at the 9-somite stage

craniorachischisis ( J:216413 )

nervous system

abnormal neural plate morphology ( J:216413 )

• broader neural plate with enlargement of the ventral midline and notochord is seen around the time of neural tube closure initiation

open neural tube ( J:216413 )

• embryos fail to initiate neural tube closure, with 100% open neural tubes at the 9-somite stage

craniorachischisis ( J:216413 )

Genotype
MGI:4948448

hm2

• Allelic Composition: Celsr1^Crsh/Celsr1^Crsh
• Genetic Background: either: (involves: 101/H * C3H/HeH) or (involves: 101/H * BALB/c * C3H/HeH)

respiratory system

abnormal lung morphology ( J:159690 )

• at E14.5 and E18.5, mutant lungs show cytokeletal defects and disordered epithelial airways with no apparent disruption of adherens junctions

• however, apical-basal polarity remains intact

abnormal branching involved in lung morphogenesis ( J:159690 )

• at E14.5, a significant reduction in the number of epithelial branches is observed

• in explant cultures, mutant E11.5 lung endoderm denuded of mesenchyme responds to a chemoattractant FGF10 stimulus in terms of growth but is unable to undergo branching

• however, no significant changes in epithelial cell differentiation are observed in vivo at E18.5

• also, no significant changes in proliferation or apoptosis are observed at E11.5 or E14.5

abnormal lung saccule morphology ( J:159690 )

• at E18.5, mutant lungs show atypical saccular structure with no evidence of septation

thick lung-associated mesenchyme ( J:159690 )

• at E18.5, mutant lungs display a thickened interstitial mesenchyme

abnormal lung epithelium morphology ( J:159690 )

• at E14.5, the mutant lung epithelium is improperly aligned and shows a multilayered and/or disorganized morphology, unlike the single layer of uniformly aligned columnar epithelium seen in wild-type lungs

• at E14.5, mutant lung epithelial cells are highly disorganized and randomly orientated with either small or no lumina, and not readily distinguishable from surrounding mesenchyme by DAPI labeling

• Celsr1^Crsh airways appeared more severely affected than Vangl2^Lp airways

abnormal lung lobe morphology ( J:159690 )

• at E18.5, mutant lung lobes are visibly misshapen

small lung lobe ( J:159690 )

• at E18.5, mutant lung lobes are smaller than wild-type lobes

small lung ( J:159690 )

• at E18.5, mutant lungs are smaller than wild-type, likely due to the reduced width and number of airway lumina and increased compaction of the lung tissue

pulmonary hypoplasia ( J:159690 )

• at E18.5, mutant lungs are hypoplastic

abnormal respiratory conducting tube morphology ( J:159690 )

• at E14.5, most airway lumina are narrow or absent

• at E18.5, the number and width of mutant airways is severely reduced while the luminal space often contains cells

impaired branching involved in terminal bronchiole morphogenesis ( J:159690 )

• after 48 hrs in ex vivo culture, mutant E11.5 lungs are smaller with significantly fewer and larger terminal buds than wild-type lungs

• addition of the Rho activator CNF-1 to mutant lung explants partially rescues the branching defect, leading to a greater increase in bud numbers than in wild-type lungs (24% vs 16%, respectively)

dilated terminal bronchiole tube ( J:159690 )

• after 48 hrs in ex vivo culture, mutant E11.5 lungs display significantly enlarged terminal buds relative to wild-type lungs

Genotype
MGI:2668349

hm3

• Allelic Composition: Celsr1^Crsh/Celsr1^Crsh
• Genetic Background: involves: 101/H * BALB/c * C3H/HeH

mortality/aging

perinatal lethality, complete penetrance ( J:84285 )

• homozygotes die perinatally, as a result of craniorachischisis

nervous system

abnormal outer hair cell kinocilium location or orientation ( J:84285 )

• in the apex at E16.5, the kinocilium is found in abnormal positions

incomplete rostral neuropore closure ( J:84285 )

• at E8.5 (~10 somite stage), homozygotes fail to initiate neural tube closure in the prospective cervical region (closure-1)

• however, neural tube closure in the forebrain and rostral midbrain occurs normally

craniorachischisis ( J:84285 , J:216413 )

• at E13.5 and E14.5, the neural tube is open from the midbrain/hindbrain boundary throughout the spine (J:84285)

• fully penetrant (J:216413)

abnormal orientation of outer hair cell stereociliary bundles ( J:84285 )

• at E18.5, homozygotes display extensive rotation of OHC stereociliary bundles along the entire length of the cochlear duct

• orientation of OHC bundles is random, including some bundles with a rotation of ~180 relative to the normal plane of orientation

• in the apex, OHC bundle misorientation is noted as early as E16.5

• in contrast, IHC stereociliary bundle orientation remains unaffected

hearing/vestibular/ear

abnormal cochlear sensory epithelium morphology ( J:84285 )

• homozygotes exhibit severe defects in planar cell polarity of the sensory epithelium

abnormal outer hair cell kinocilium location or orientation ( J:84285 )

• in the apex at E16.5, the kinocilium is found in abnormal positions

abnormal orientation of outer hair cell stereociliary bundles ( J:84285 )

• in the apex, OHC bundle misorientation is noted as early as E16.5

• at E18.5, homozygotes display extensive rotation of OHC stereociliary bundles along the entire length of the cochlear duct

• orientation of OHC bundles is random, including some bundles with a rotation of ~180 relative to the normal plane of orientation

• in contrast, IHC stereociliary bundle orientation remains unaffected

vision/eye

absent eyelids ( J:84285 )

• homozygous fetuses often exhibit a delay or failure of eyelid closure

• at E17.5, homozygotes exhibit absence of eyelids

embryo

incomplete rostral neuropore closure ( J:84285 )

• at E8.5 (~10 somite stage), homozygotes fail to initiate neural tube closure in the prospective cervical region (closure-1)

• however, neural tube closure in the forebrain and rostral midbrain occurs normally

craniorachischisis ( J:84285 , J:216413 )

• at E13.5 and E14.5, the neural tube is open from the midbrain/hindbrain boundary throughout the spine (J:84285)

• fully penetrant (J:216413)

cellular

abnormal outer hair cell kinocilium location or orientation ( J:84285 )

• in the apex at E16.5, the kinocilium is found in abnormal positions

Genotype
MGI:5661735

ht4

• Allelic Composition: Celsr1^Crsh/Celsr1⁺
• Genetic Background: C3H.Cg-Celsr1^Crsh

behavior/neurological

head shaking ( J:216413 )

• Background Sensitivity: shaky-head behavior becomes less penetrant on the C3H/HeH background, seen in 32% of mice

embryo

delayed neural tube closure ( J:216413 )

• embryos exhibit delayed neural tube closure, of about 1.3 somite stages compared to wild-type, however, all embryos initiate closure by the 9-somite stage

nervous system

delayed neural tube closure ( J:216413 )

• embryos exhibit delayed neural tube closure, of about 1.3 somite stages compared to wild-type, however, all embryos initiate closure by the 9-somite stage

Genotype
MGI:2668352

ht5

• Allelic Composition: Celsr1^Crsh/Celsr1⁺
• Genetic Background: involves: 101/H * BALB/c * C3H/HeH

behavior/neurological

head shaking ( J:84285 , J:216413 )

• Background Sensitivity: shaky-head behavior is more penetrant, seen in 68% of mice, compared to mice on a congenic C3H/HeH background in which 32% exhibit this phenotype (J:216413)

spinning ( J:84285 )

• heterozygotes exhibit belly curling and spinning during tail suspension

• however, no obvious peripheral vestibular defects are detected in adulthood

hearing/vestibular/ear

abnormal cochlear sensory epithelium morphology ( J:84285 )

• heterozygotes exhibit a positive Preyer's reflex in response to a 20 kHz, 90 dB SPL tone burst, indicating that they are not profoundly deaf

• however, heterozygotes show mild defects in planar cell polarity of the sensory epithelium

abnormal orientation of outer hair cell stereociliary bundles ( J:84285 )

• adult heterozygotes display mildly misoriented OHC stereociliary bundles in the apical cochlear relative to Celsr1^Scy heterozygotes, with fewer OHCs being affected

• in contrast, IHC stereociliary bundle orientation remains unaffected

nervous system

abnormal orientation of outer hair cell stereociliary bundles ( J:84285 )

• adult heterozygotes display mildly misoriented OHC stereociliary bundles in the apical cochlear relative to Celsr1^Scy heterozygotes, with fewer OHCs being affected

• in contrast, IHC stereociliary bundle orientation remains unaffected

Genotype
MGI:3690972

ht6

• Allelic Composition: Celsr1^Crsh/Celsr1^Scy
• Genetic Background: involves: 101/H * BALB/c * C3H/He * C3H/HeH

nervous system

craniorachischisis ( J:84285 )

• at E13.5, craniorachischisis is indistinguishable from that of single homozygotes

embryo

craniorachischisis ( J:84285 )

• at E13.5, craniorachischisis is indistinguishable from that of single homozygotes

Genotype
MGI:5661818

cx7

• Allelic Composition: Celsr1^Crsh/Celsr1⁺; Scrib^Crc/Scrib⁺
• Genetic Background: C3H.Cg-Scrib^Crc Celsr1^Crsh

embryo

abnormal developmental patterning ( J:216413 )

• skewed body axis in some mutants

spina bifida ( J:216413 )

• lumbosacral open spina bifida in 2% of mutants (1 of 41); this mouse shows partially closed eyelids

craniorachischisis ( J:216413 )

• 42% of mutants exhibit craniorachischisis, most often isolated (32% of mutants) but sometimes associated with abdominal wall defect and a skewed body axis (10% of mutants)

• however, 46% of mutants appear normal

growth/size/body

abnormal abdominal wall morphology ( J:216413 )

• abdominal wall defect in some mutants

limbs/digits/tail

curly tail ( J:216413 )

• 2% of mutants exhibit a looped tail

nervous system

spina bifida ( J:216413 )

• lumbosacral open spina bifida in 2% of mutants (1 of 41); this mouse shows partially closed eyelids

craniorachischisis ( J:216413 )

• 42% of mutants exhibit craniorachischisis, most often isolated (32% of mutants) but sometimes associated with abdominal wall defect and a skewed body axis (10% of mutants)

• however, 46% of mutants appear normal

exencephaly ( J:216413 )

• isolated exencephaly in 7% of mutants

vision/eye

abnormal eyelid morphology ( J:216413 )

• mutants with craniorachischisis show completely open eyelids at E16.5

abnormal eyelid development ( J:216413 )

• 50% of mutants (5 of 10) exhibit failure of eyelid formation at E16.5

• mutants with craniorachischisis show completely open eyelids

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neural tube defect		DOID:0080074	OMIM:301410 OMIM:601634	J:216413

Genotype
MGI:5661740

cx8

• Allelic Composition: Celsr1^Crsh/Celsr1⁺; Vangl2^Lp/Vangl2⁺
• Genetic Background: C3H.Cg-Vangl2^Lp Celsr1^Crsh

embryo

abnormal left-right axis patterning ( J:216413 )

• rightward skewing of the embryo, with shortening of the right-hand size compared with the left, suggesting a defect in embryo turning

craniorachischisis ( J:216413 )

• 100% of embryos exhibit craniorachischisis, occurring usually as an isolated defect (in 89% of mutants) but sometimes associated with an abdominal wall defect (in 11% of mutants)

growth/size/body

omphalocele ( J:216413 )

• abdominal wall defect in 11% of mutants, which is likely to be omphalocele/exomphalos

nervous system

craniorachischisis ( J:216413 )

• 100% of embryos exhibit craniorachischisis, occurring usually as an isolated defect (in 89% of mutants) but sometimes associated with an abdominal wall defect (in 11% of mutants)

vision/eye

abnormal eyelid morphology ( J:216413 )

• 3 of 5 mutants fail to close eyelids at E16.5, while others show partial eyelid closure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neural tube defect		DOID:0080074	OMIM:301410 OMIM:601634	J:216413

Genotype
MGI:5661822

cx9

• Allelic Composition: Celsr1^Crsh/Celsr1⁺; Scrib^Crc/Scrib⁺; Vangl2^Lp/Vangl2⁺
• Genetic Background: C3H.Cg-Vangl2^Lp Scrib^Crc Celsr1^Crsh

embryo

craniorachischisis ( J:216413 )

• 2 of 3 mutants exhibit craniorachischisis

limbs/digits/tail

abnormal tail morphology ( J:216413 )

• 1 of 3 mice exhibits hindbrain exencephaly and a tail defect

nervous system

craniorachischisis ( J:216413 )

• 2 of 3 mutants exhibit craniorachischisis

exencephaly ( J:216413 )

• 1 of 3 mice exhibits hindbrain exencephaly and a tail defect

Genotype
MGI:4830334

cx10

• Allelic Composition: Celsr1^Crsh/Celsr1⁺; Ptk7^chz/Ptk7⁺
• Genetic Background: involves: 101/H * BALB/c * BALB/cAnN * C3H/HeH

embryo

spina bifida ( J:163834 )

• 6% display spina bifida

nervous system

spina bifida ( J:163834 )

• 6% display spina bifida

Genotype
MGI:5661724

cx11

• Allelic Composition: Celsr1^Crsh/Celsr1⁺; Scrib^Crc/Scrib⁺
• Genetic Background: involves: 101/H * BALB/c * C3H/HeH * C57BL/6 * NMRI

embryo

craniorachischisis ( J:216413 )

• 8% of embryos develop craniorachischisis

nervous system

craniorachischisis ( J:216413 )

• 8% of embryos develop craniorachischisis

Genotype
MGI:5661720

cx12

• Allelic Composition: Celsr1^Crsh/Celsr1⁺; Vangl2^Lp/Vangl2⁺
• Genetic Background: involves: 101/H * BALB/c * C3H/HeH * CBA * LPT/Le

embryo

craniorachischisis ( J:216413 )

• 54% of embryos develop craniorachischisis

limbs/digits/tail

curly tail ( J:216413 )

• the mice that do not develop craniorachischisis exhibit a looped tail

nervous system

craniorachischisis ( J:216413 )

• 54% of embryos develop craniorachischisis