Mouse Genome Informatics
hm
    Smpd3fro/Smpd3fro
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 8.8% of mutants survive past birth (J:3906)
• only 10% of mice survive to live a normal lifespan and breed normally (J:6711)
• survivors remain small and deformed (J:6711)
• 91.25% of mutants with deformities die at birth or within a day or two of birth (J:3906)
• 90% of homozygous mice die before day 3 (J:6711)

growth/size
• delayed formation of dentin in the incisor
• runted at birth (J:6711)
• smaller at birth (J:100158)
• surviving mutants exhibit shorter total body length life, with total length 84% of normal at 45 days of age

homeostasis/metabolism
• probably in response to reduced calcium stores in bone (J:7673)
• mice that die are cyanotic and breathe in short irregular gasps

limbs/digits/tail
• deformities of all four limbs
• mice exhibit severe skeletal deformities of all four limbs at birth, mainly consisting of bowing of the long bones
• surviving mice show gradual straightening of the long bones once they survive the neonatal period
• humerus is short with irregular metaphyseal borders and poor corticomedullary demarcation
• humerus is reduced in length by about one-third; reduction is distal to the deltoid tuberosity
• proximal and distal segments grow at the same rate as in controls but remain smaller throughout life
• total length of the humerus is 64% of normal at 45 days of age
• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaft
• some surviving mice exhibit bowed radii
• ulna is characterized by a long zone of increased ossification corresponding to the olecranon
• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaf
• some surviving mice exhibit bowed ulnae
• proximal segment of the ulna has normal growth rate but little growth takes place postnatally at the distal end
• length of the ulna is 60% of normal at 45 days of age
• femur is characterized by a constriction halfway along its length and rounding of the ends (dumbbell appearance) in both nonsurviving mice and most surviving mice
• femur is crumpled and about 1/2 to 1/3 its normal length at birth
• from P1-P15, femur is shorter and transverse trabeculae are visible throughout the diaphysis, however it is not bowed
• fibula is the least affected of the long bones, showing little bowing, crumbling or irregular ossification centers but is underossified
• tibia has a crumbly texture with concertina appearance and is constricted at a point [?] from the distal end in nonsurviving mutants
• from P1-P15, tibia is bowed with thin cortices and broad metaphyses in surviving mutants
• surviving mutants show deformed tibiae, with variable degree of bowing

skeleton
• defective alveolar bone mineralization
• mice exhibit severe skeletal deformities of all four limbs at birth, mainly consisting of bowing of the long bones
• surviving mice show gradual straightening of the long bones once they survive the neonatal period
• tibia, femur, and humerus are the most severely deformed bones (J:3906)
• all long bones are short, curved and show fractures (J:6711)
• multiple fractures of long bones at birth (J:100158)
• humerus is short with irregular metaphyseal borders and poor corticomedullary demarcation
• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaft
• some surviving mice exhibit bowed radii
• ulna is characterized by a long zone of increased ossification corresponding to the olecranon
• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaf
• some surviving mice exhibit bowed ulnae
• femur is characterized by a constriction halfway along its length and rounding of the ends (dumbbell appearance) in both nonsurviving mice and most surviving mice
• fibula is the least affected of the long bones, showing little bowing, crumbling or irregular ossification centers but is underossified
• tibia has a crumbly texture with concertina appearance and is constricted at a point [?] from the distal end in nonsurviving mutants
• from P1-P15, tibia is bowed with thin cortices and broad metaphyses in surviving mutants
• surviving mutants show deformed tibiae, with variable degree of bowing
• clavicle is frequently bowed at the sternal end
• surviving mutants show a broad tibial metaphysis at P1-P15
• humerus exhibits an irregular metaphysis border
• bones show fewer trabeculae within the metaphysis
• bones are also curved
• humerus is reduced in length by about one-third; reduction is distal to the deltoid tuberosity
• proximal and distal segments grow at the same rate as in controls but remain smaller throughout life
• total length of the humerus is 64% of normal at 45 days of age
• proximal segment of the ulna has normal growth rate but little growth takes place postnatally at the distal end
• length of the ulna is 60% of normal at 45 days of age
• femur is crumpled and about 1/2 to 1/3 its normal length at birth
• from P1-P15, femur is shorter and transverse trabeculae are visible throughout the diaphysis, however it is not bowed
• scapulae are always bowed
• the ischium is bowed at the midline
• the pubis is bowed at the midline
• ribs are wavy in mutants that die at or shortly after birth, exhibiting 1-3 bows along their length
• surviving mutants do not show wavy ribs or rib angulation deformities and tend to have rib cages of normal configuration
• multiple fractures of ribs at birth
• from P1-P15, scapulae appears normal in shape but is oteopenic
• P15 mutants exhibit persistent osteopenia, bowing of the forearm bones and angulation deformity of legs
• P45, mutants show slightly less bowing of forearms but still show persistent osteopenia
• osteoblasts exhibit dilated rough endoplastic reticulum and the cisternae are more densely packed with particulate matter
• the layers of the perichondrium/periosteum are more widely separated in in neonates than controls
• bones show fewer trabeculae within the metaphysis and the collar is thickened on the inner side of the bone where bowing is present
• initiation and progress is normal but osteoid
• the layers of the perichondrium/periosteum are more widely separated in in neonates than controls
• the growth line in some areas shows islands of cartilage adjacent to the zone of chondrosseous transformation
• bulk of the length of shortened bone is made up substantially of two enlarged growth plates
• general organization of the growth plate is normal in 1 day old mutants, however the hypertrophic zone is wider, about 3-4 times that of the controls
• skeleton of 1 day old mutants is poorly ossified throughout, including the skull vault, base, facial skeleton, vertebrae, ribs, sternum, and long bones
• ossification centers are irregular and occupy 1/5 of the entire length of the radius and ulna
• nonsurviving mice show skeletal defects similar to osteogenesis imperfect, type IIA
• surviving mice show skeletal defects similar to osteogenesis imperfect, type IIB or III
• sternum is normal in shape but fewer sternabrae are ossified
• bone is severely undermineralized (J:7673)
• matrix of developing bones is severely undermineralized (J:100158)
• defective alveolar bone mineralization (J:100158)
• severe tooth and alveolar bone abnormalities due to impaired mineralization (J:100158)
• delay in ossification of a number of secondary ossification centers, with the olecranon, head of humerus, distal end of femur, proximal and distal ends of both the fibula and tibia appearing later

reproductive system
• mice are poor breeders

respiratory system
• mice that die are cyanotic and breathe in short irregular gasps

craniofacial
• defective alveolar bone mineralization
• delayed formation of dentin in the incisor

Mouse Models of Human Disease
OMIM IDRef(s)
Osteogenesis Imperfecta, Type II 166210 J:3906
Osteogenesis Imperfecta, Type III 259420 J:3906