Phenotypes Associated with This Genotype

Genotype
MGI:5693602

• Allelic Composition: Cilk1^{tm1a(KOMP)Mbp}/Cilk1^{tm1a(KOMP)Mbp}
• Genetic Background: C57BL/6N-Cilk1^{tm1a(KOMP)Mbp}
• Cell Lines: DEPD00524_1_A09

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

Endocrine-cerebro-osteodysplasia syndrome-like features in Cilk1^{tm1a(KOMP)Mbp}/Cilk1^{tm1a(KOMP)Mbp} mice

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:211652 )

• homozygotes generally show embryonic lethality at late stages of gestation with unknown cause

growth/size/body

cleft palate ( J:211652 )

• at E15.5, mutant embryos show cleft palates in the roof of the oral cavity

abnormal tongue morphology ( J:211652 )

• at E15.5, mutant tongues are malformed

decreased tongue size ( J:211652 )

• at E15.5, mutant tongues are smaller than wild type

homeostasis/metabolism

edema ( J:211652 )

• at E15.5, mutant embryos exhibit extensive edema at the head and back

limbs/digits/tail

preaxial polydactyly ( J:211652 )

• at E15.5, mutant forelimbs exhibit polydactyly

abnormal ulna morphology ( J:211652 )

• mutant embryos exhibit deviated ulnar formation

abnormal digit development ( J:211652 )

• at E18.5, alcian blue/alizarin red staining revealed delayed ossification in the digits

• mutant embryos exhibit elongated primary cilia and reduced Shh signaling during limb digit patterning

short limbs ( J:211652 )

• at E18.5

skeleton

abnormal long bone morphology ( J:211652 )

• at E18.5, mutant long bones are severely distorted and shortened

abnormal ulna morphology ( J:211652 )

• mutant embryos exhibit deviated ulnar formation

decreased length of long bones ( J:211652 )

• at E18.5

abnormal skeleton development ( J:211652 )

• mutant embryos show delayed skeletal development

abnormal bone mineralization ( J:211652 )

• at E18.5, mutant embryos exhibit reduced bone mineralization

delayed bone ossification ( J:211652 )

• at E18.5, alcian blue/alizarin red staining revealed delayed ossification in the digits

nervous system

nervous system phenotype ( J:211652 )

N • at E10.5, homozygotes show normal ventral neural tube patterning, as determined by Shh-regulated neuronal cell identity markers

hydrocephaly ( J:211652 )

dilated brain ventricle ( J:211652 )

• at E15.5, mutant embryos display severely dilated ventricles in the developing telencephalon

digestive/alimentary system

cleft palate ( J:211652 )

• at E15.5, mutant embryos show cleft palates in the roof of the oral cavity

abnormal tongue morphology ( J:211652 )

• at E15.5, mutant tongues are malformed

decreased tongue size ( J:211652 )

• at E15.5, mutant tongues are smaller than wild type

craniofacial

cleft palate ( J:211652 )

• at E15.5, mutant embryos show cleft palates in the roof of the oral cavity

abnormal tongue morphology ( J:211652 )

• at E15.5, mutant tongues are malformed

decreased tongue size ( J:211652 )

• at E15.5, mutant tongues are smaller than wild type

renal/urinary system

abnormal kidney development ( J:211652 )

• at E16.5, mutant kidneys show cyst-like tubule expansion

cellular

abnormal primary cilium morphology ( J:211652 )

• at E11.5, primary cilia in mutant limb buds are 2.5-fold longer than those in wild type limb buds

• scanning EM confirmed that primary cilia in the mutant limb ectoderm are significantly longer relative to wild-type controls

• however, transmission EM showed normal primary cilia ultrastructure in the limb mesenchyme at the level of basal body or axoneme

• no defects in ciliary formation are observed in the spinal neural tube at E10.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endocrine-cerebro-osteodysplasia syndrome		DOID:0060641	OMIM:612651	J:211652