Phenotypes associated with this allele

• Allele Symbol: Acan^cmd
• Allele Name: cartilage matrix deficiency
• Allele ID: MGI:1856465
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Acan^cmd/Acan^cmd	involves: STOCK T t^low Itpr3^tf	MGI:3694235
hm2	Acan^cmd/Acan^cmd	STOCK T t^low Itpr3^tf	MGI:3694230
ht3	Acan^cmd/Acan^+	involves: STOCK T t^low Itpr3^tf	MGI:2675624

Genotype
MGI:3694235

hm1

• Allelic Composition: Acan^cmd/Acan^cmd
• Genetic Background: involves: STOCK T t^low Itpr3^tf

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

mortality/aging

neonatal lethality, complete penetrance ( J:553 )

• die due to breathing failure just after birth

hearing/vestibular/ear

abnormal organ of Corti morphology ( J:553 )

• in organ of Corti, high density cystic formations are observed in Nuel's space and the tunnel of Corti

absent cochlear outer hair cells ( J:553 )

• hair cells are absent in the first cochlear turn and in organ of Corti

abnormal cochlear inner hair cell morphology ( J:553 )

• hair cells are fused

abnormal cochlear IHC afferent innervation pattern ( J:553 )

• no nerve fibers or nerve endings are observed in the first cochlear turn

increased or absent threshold for auditory brainstem response ( J:553 )

• responses can not be evoked with stimuli under 80 db

deafness ( J:553 )

• homozygotes display marked hearing loss

growth/size/body

cleft palate ( J:553 )

small thoracic cavity ( J:23353 )

• thoracic cavity volume is decreased by 38%

disproportionate dwarf ( J:553 )

• disproportionate, dwarfed stature

• short trunks, limbs, tails, snout

homeostasis/metabolism

polyhydramnios ( J:23353 )

• volume of amniotic fluid is 8 times greater in mutants on E18

respiratory system

abnormal lung morphology ( J:23353 )

• at E18, primary saccules are more numerous, appear compressed and parenchymal cells are less organized

pulmonary hypoplasia ( J:23353 )

• at E18, lungs are smaller than wild-type but normal in shape

nervous system

absent cochlear outer hair cells ( J:553 )

• hair cells are absent in the first cochlear turn and in organ of Corti

abnormal cochlear inner hair cell morphology ( J:553 )

• hair cells are fused

abnormal cochlear IHC afferent innervation pattern ( J:553 )

• no nerve fibers or nerve endings are observed in the first cochlear turn

craniofacial

cleft palate ( J:553 )

digestive/alimentary system

cleft palate ( J:553 )

skeleton

abnormal cartilage development ( J:1535 )

• abnormally high fibronectin production by chrondrocytes results in aberrant cartilage

• in chondrocyte cultures, the defects in the cartilage produced can be ameliorated by the addition of cartilage proteoglycan monomer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondroplasia		DOID:4480	OMIM:100800	J:5952 , J:30795

Genotype
MGI:3694230

hm2

• Allelic Composition: Acan^cmd/Acan^cmd
• Genetic Background: STOCK T t^low Itpr3^tf

mortality/aging

neonatal lethality, complete penetrance ( J:5952 )

• homozygotes are born alive, but die shortly after birth due to inability to breathe

growth/size/body

cleft palate ( J:5952 , J:30795 )

protruding tongue ( J:5952 )

flattened snout ( J:5952 )

• snout is short and blunted

short snout ( J:5952 )

disproportionate dwarf ( J:30795 )

• noted at birth

distended abdomen ( J:5952 , J:30795 )

• abdomen is strikingly protruberant (J:5952)

• newborns display distended abdomens (J:30795)

enlarged liver ( J:5952 )

• liver is enlarged, likely due to congestion with blood

craniofacial

abnormal craniofacial bone morphology ( J:30795 )

• facial bones are reduced in antero-posterior length at E18

short basicranium ( J:30795 )

• cranial base is reduced in antero-posterior length at E18

cleft palate ( J:5952 , J:30795 )

protruding tongue ( J:5952 )

flattened snout ( J:5952 )

• snout is short and blunted

short snout ( J:5952 )

skeleton

abnormal craniofacial bone morphology ( J:30795 )

• facial bones are reduced in antero-posterior length at E18

short basicranium ( J:30795 )

• cranial base is reduced in antero-posterior length at E18

abnormal tracheal cartilage morphology ( J:5952 )

• chondrocytes are tightly packed, there is very little matrix and many pyknotic cells, which often contain vacuoles

decreased length of long bones ( J:5952 )

• long bones are reduced to >50% of normal length

short humerus ( J:5952 )

short femur ( J:5952 )

abnormal rib morphology ( J:30795 )

• ribs are short and blunted at E18

abnormal vertebrae morphology ( J:5952 , J:30795 )

• three calcification centers (one in vertebral body, one in each half of vertebral arch) are joined except in most posterior calcified vertebrae while these centers are well defined in the wild-type vertebrae (J:5952)

absent caudal vertebrae ( J:30795 )

• number of tail vertebrae is reduced at E18

short vertebral column ( J:5952 , J:30795 )

• spinal column is shortened by ~25% (mutants 15.4 mm vs wild-type 21.4 mm in length) (J:5952)

• axial skeleton is shortened at E18 (J:30795)

abnormal trabecular bone morphology ( J:30795 )

• in E16 mutants, spongy bone is present throughout the width of the bone shaft, whereas in wild-type, it is confined to periosteum

abnormal cartilage development ( J:30795 )

• cartilage shows reduced growth rate starting at ~E13

• cartilage in all parts of skeleton is abnormal by E14

abnormal chondrocyte morphology ( J:5952 , J:30795 )

• mutant cells have few short and blunt cytoplasmic processes (J:5952)

• in E16 limb bones, chondrocytes start to undergo degenerative changes (J:30795)

limbs/digits/tail

abnormal limb morphology ( J:30795 )

• mutants can be identified by E15 because of shortened limbs

• in E18 mutants, limb girdles and long bones are ~half of normal size

brachydactyly ( J:30795 )

short humerus ( J:5952 )

short femur ( J:5952 )

absent caudal vertebrae ( J:30795 )

• number of tail vertebrae is reduced at E18

liver/biliary system

abnormal liver morphology ( J:5952 )

• in newborns, and to lesser extent in embryos, livers are darker than normal

enlarged liver ( J:5952 )

• liver is enlarged, likely due to congestion with blood

respiratory system

abnormal tracheal cartilage morphology ( J:5952 )

• chondrocytes are tightly packed, there is very little matrix and many pyknotic cells, which often contain vacuoles

respiratory distress ( J:5952 )

digestive/alimentary system

cleft palate ( J:5952 , J:30795 )

protruding tongue ( J:5952 )

Genotype
MGI:2675624

ht3

• Allelic Composition: Acan^cmd/Acan⁺
• Genetic Background: involves: STOCK T t^low Itpr3^tf

Radiographs of wild-type and Acan^cmd/Acan⁺ mice

mortality/aging

premature death ( J:41498 )

• no heterozygotes live longer than 19 months

growth/size/body

disproportionate dwarf ( J:41498 )

• slight dwarfism seen about 28 days after birth

behavior/neurological

aphagia ( J:41498 )

• mutants cannot eat and starve within 1 month of developing the abnormal gait

abnormal gait ( J:41498 )

• develop spastic gait and show decreased movement with sudden onset

nervous system

abnormal spinal cord morphology ( J:41498 )

• oppression of the spinal cord by herniated disk

skeleton

abnormal intervertebral disk morphology ( J:41498 )

• herniation of vertebral disks

intervertebral disk degeneration ( J:41498 )

• the chondrocytes of vertebral disks show degeneration and are abnormally packed and the extracellular matrix shows concentric dense bundle patterns instead of a fine diffuse pattern

kyphosis ( J:41498 )

• in the thoraco-lumbar spine

lordosis ( J:41498 )

• in the cervical spine

abnormal vertebral body morphology ( J:41498 )

• disappearance of apophyseal cartilage and deformation of vertebral bodies