Mouse Genome Informatics
hm1
    Acancmd/Acancmd
involves: STOCK T tlow Itpr3tf
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die due to breathing failure just after birth

hearing/vestibular/ear
• in organ of Corti, high density cystic formations are observed in Nuel's space and the tunnel of Corti
• hair cells are absent in the first cochlear turn and in organ of Corti
• no nerve fibers or nerve endings are observed in the first cochlear turn
• responses can not be evoked with stimuli under 80 db
• homozygotes display marked hearing loss

growth/size
• thoracic cavity volume is decreased by 38%
• disproportionate, dwarfed stature
• short trunks, limbs, tails, snout

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

respiratory system
• at E18, primary saccules are more numerous, appear compressed and parenchymal cells are less organized
• at E18, lungs are smaller than wild-type but normal in shape

nervous system
• hair cells are absent in the first cochlear turn and in organ of Corti
• no nerve fibers or nerve endings are observed in the first cochlear turn

craniofacial

digestive/alimentary system

skeleton
• 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
OMIM IDRef(s)
Achondroplasia; ACH 100800 J:5952 , J:30795


Mouse Genome Informatics
hm2
    Acancmd/Acancmd
STOCK T tlow Itpr3tf
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes are born alive, but die shortly after birth due to inability to breathe

growth/size
• noted at birth
• abdomen is strikingly protruberant (J:5952)
• newborns display distended abdomens (J:30795)

craniofacial
• facial bones are reduced in antero-posterior length at E18
• cranial base is reduced in antero-posterior length at E18
• snout is short and blunted

skeleton
• facial bones are reduced in antero-posterior length at E18
• cranial base is reduced in antero-posterior length at E18
• chondrocytes are tightly packed, there is very little matrix and many pyknotic cells, which often contain vacuoles
• long bones are reduced to >50% of normal length
• ribs are short and blunted at E18
• 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)
• number of tail vertebrae is reduced at E18
• 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)
• in E16 mutants, spongy bone is present throughout the width of the bone shaft, whereas in wild-type, it is confined to periosteum
• cartilage shows reduced growth rate starting at ~E13
• cartilage in all parts of skeleton is abnormal by E14
• 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
• mutants can be identified by E15 because of shortened limbs
• in E18 mutants, limb girdles and long bones are ~half of normal size
• number of tail vertebrae is reduced at E18

liver/biliary system
• in newborns, and to lesser extent in embryos, livers are darker than normal
• liver is enlarged, likely due to congestion with blood

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

digestive/alimentary system


Mouse Genome Informatics
ht3
    Acancmd/Acan+
involves: STOCK T tlow Itpr3tf
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Radiographs of wild-type and Acancmd/Acan+ mice

mortality/aging
• no heterozygotes live longer than 19 months

growth/size
• slight dwarfism seen about 28 days after birth

behavior/neurological
• mutants cannot eat and starve within 1 month of developing the abnormal gait
• develop spastic gait and show decreased movement with sudden onset

nervous system
• oppression of the spinal cord by herniated disk

skeleton
• herniation of vertebral disks
• 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
• in the thoraco-lumbar spine
• in the cervical spine
• disappearance of apophyseal cartilage and deformation of vertebral bodies