Phenotypes Associated with This Genotype

Genotype
MGI:6759479

• Allelic Composition: Cilk1^tm1.1Zfu/Cilk1^tm1.1Zfu
• Genetic Background: B6.Cg-Cilk1^tm1.1Zfu/Zfu

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

mortality/aging

neonatal lethality, complete penetrance ( J:309653 )

• mice die shortly after birth due to respiratory failure

craniofacial

increased mouth size ( J:309376 )

• bigger mouth

small snout ( J:309376 )

broad head ( J:309376 )

respiratory system

decreased mesenchymal cell proliferation involved in lung development ( J:309653 )

• lungs show a decrease in the number of proliferating mesenchymal, but not epithelial, cells at E12.5

abnormal branching involved in lung morphogenesis ( J:309653 )

• the number of lung buds per area is reduced by about 50% in embryos at E12.5-E13.5, indicating that lung branching morphogenesis is reduced

abnormal lung alveolus development ( J:309653 )

• formation of alveolar precursors is severely disrupted

• however, lungs have both alveolar type 1 and type 2 cells and secreted surfactants in airspace, indicating that differentiation of alveolar epithelial cells in primitive alveoli is normal

abnormal lung bud morphology ( J:309653 )

• the number of lung buds per area is reduced by about 50% in embryos at E12.5-E13.5

abnormal lung saccule morphology ( J:309653 )

• lungs exhibit a reduction in the lung saccular area

abnormal lung-associated mesenchyme development ( J:309653 )

• lungs exhibit an increase of smooth muscle actin-positive mesenchymal cells in the thickened interstitium

thick lung-associated mesenchyme ( J:309653 )

• lungs exhibit an increase in mesenchymal thickness

pulmonary hypoplasia ( J:309653 )

• lungs are hypoplastic and severely deficient in airspace

respiratory failure ( J:309653 )

• mice show inadequate oxygenation of lungs and die due to respiratory failure

growth/size/body

increased mouth size ( J:309376 )

• bigger mouth

small snout ( J:309376 )

broad head ( J:309376 )

abnormal chest morphology ( J:309376 )

• shorter thorax

abnormal neck morphology ( J:309376 )

• increase in neck-spine angle

short neck ( J:309376 )

limbs/digits/tail

polydactyly ( J:309376 , J:309653 )

• polydactyly is seen in both forelimb and hindlimb with an average of 6.5 digits (J:309376)

abnormal tarsal bone morphology ( J:309376 )

• tarsal bones are deformed at E15.5

abnormal hindlimb morphology ( J:309376 )

• flat ankles

short femur ( J:309376 )

• E18.5 femurs are shorter

short limbs ( J:309376 , J:309653 )

nervous system

abnormal cervical flexure morphology ( J:309376 )

• broader cervical flexure

skeleton

abnormal tarsal bone morphology ( J:309376 )

• tarsal bones are deformed at E15.5

abnormal long bone morphology ( J:309376 )

• limb bones are deformed at E15.5

• bowed long bones

abnormal long bone epiphyseal plate proliferative zone ( J:309376 )

• reduction in proliferative chondrocyte zone

• however, the hypertrophic chondrocyte zone is normal

decreased length of long bones ( J:309376 )

• the longitudinal length of long bones is reduced

short femur ( J:309376 )

• E18.5 femurs are shorter

abnormal thoracic cage morphology ( J:309376 )

• underdeveloped rib cage

abnormal vertebral column morphology ( J:309376 )

• severe defects in the spinal column

abnormal intervertebral disk morphology ( J:309376 )

• the intervertebral disk is deformed

absent nucleus pulposus ( J:309376 )

• intervertebral disk is without a clear nucleus pulposus structure

abnormal vertebrae morphology ( J:309376 )

• vertebrae are much narrower, irregularly shaped, and severely distorted

abnormal intervertebral disk development ( J:309376 )

• intervertebral disks are underdeveloped, without a clear nucleus pulposus structure and annulus fibrosus

abnormal vertebral transverse process morphology ( J:309376 )

• transverse processes are severely distorted

abnormal chondrocyte differentiation ( J:309376 )

• marker analysis indicates impaired chondrocyte maturation in both the spine and long bones

decreased bone mineralization ( J:309376 )

• mice show reduced mineralization in the spinal column, ribs, and long bones

abnormal endochondral bone ossification ( J:309376 )

• endochondral bone is barely detectable in E15.5 femurs and at least 50% shorter than that of wild-type in E18.5 femurs

decreased bone ossification ( J:309376 )

• bone ossification is reduced in femurs

homeostasis/metabolism

enhanced autophagy ( J:309653 )

• marker analysis indicates an increase in basal autophagy in the lungs

• MEFs exhibit faster autophagy flux and quicker degradative process in both the steady-state and starvation conditions

cellular

abnormal primary cilium morphology ( J:309653 )

• embryonic lungs exhibit elongated primary cilia

• mouse embryonic fibroblasts exhibit elongation of primary cilium

enhanced autophagy ( J:309653 )

• marker analysis indicates an increase in basal autophagy in the lungs

• MEFs exhibit faster autophagy flux and quicker degradative process in both the steady-state and starvation conditions

decreased mesenchymal cell proliferation involved in lung development ( J:309653 )

• lungs show a decrease in the number of proliferating mesenchymal, but not epithelial, cells at E12.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endocrine-cerebro-osteodysplasia syndrome		DOID:0060641	OMIM:612651	J:309376 , J:309653