Phenotypes associated with this allele

• Allele Symbol: Smpd3^fro
• Allele Name: fragilitas ossium
• Allele ID: MGI:1856877
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smpd3^fro/Smpd3^fro	B6N.Cg-Smpd3^fro	MGI:5493426
hm2	Smpd3^fro/Smpd3^fro	C3H.Cg-Smpd3^fro	MGI:5493427
hm3	Smpd3^fro/Smpd3^fro	involves: C3H/HeN * C57BL/6N	MGI:5493419
hm4	Smpd3^fro/Smpd3^fro	Not Specified	MGI:4437913

Genotype
MGI:5493426

hm1

• Allelic Composition: Smpd3^fro/Smpd3^fro
• Genetic Background: B6N.Cg-Smpd3^fro

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:193949 )

• Background Sensitivity: 35% survival rate at weaning on the C57BL/6N background compared to 57% survival on the C3H/HeN background and 88% on a mixed C57BL/6N and C3H/HeN background

Genotype
MGI:5493427

hm2

• Allelic Composition: Smpd3^fro/Smpd3^fro
• Genetic Background: C3H.Cg-Smpd3^fro

mortality/aging

postnatal lethality, incomplete penetrance ( J:193949 )

• 57% survival rate at weaning on the C3H/HeN background compared to 35% survival on the C57BL/6N background and 88% on a mixed C57BL/6N and C3H/HeN background

Genotype
MGI:5493419

hm3

• Allelic Composition: Smpd3^fro/Smpd3^fro
• Genetic Background: involves: C3H/HeN * C57BL/6N

mortality/aging

postnatal lethality, incomplete penetrance ( J:193949 )

• Background Sensitivity: 88% of mutants survive past weaning; this survival rate is much higher than on either the C57BL/6N or C3H/HeN congenic background

limbs/digits/tail

abnormal limb morphology ( J:193949 )

• limb deformities

respiratory system

abnormal pulmonary alveolus morphology ( J:193949 )

• increase in mean linear intercept, indicating greater distance between alveolar septa across the lungs and fewer septa

overexpanded pulmonary alveolus ( J:193949 )

• increase in distal airspace size in 6 week old mutants

emphysema ( J:193949 )

• increase in the number of alveoli showing emphysematous changes, indicating development of a lung disorder similar to emphysema

increased lung compliance ( J:193949 )

• mutants show increased compliance of the respiratory system

homeostasis/metabolism

abnormal lipid level ( J:193949 )

• decrease in the level of ceramide C14:0 in the lungs and bone

Genotype
MGI:4437913

hm4

• Allelic Composition: Smpd3^fro/Smpd3^fro
• Genetic Background: Not Specified

mortality/aging

decreased survivor rate ( J:3906 , J:6711 )

• 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)

postnatal lethality, incomplete penetrance ( J:3906 , 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/body

abnormal alveolar process morphology ( J:100158 )

• defective alveolar bone mineralization

abnormal dentin development ( J:100158 )

• delayed formation of dentin in the incisor

decreased body size ( J:6711 , J:100158 )

• runted at birth (J:6711)

• smaller at birth (J:100158)

decreased body length ( J:3906 )

• surviving mutants exhibit shorter total body length life, with total length 84% of normal at 45 days of age

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:7673 , J:100158 )

• probably in response to reduced calcium stores in bone (J:7673)

cyanosis ( J:3906 )

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

limbs/digits/tail

abnormal limb morphology ( J:6711 )

• deformities of all four limbs

abnormal limb bone morphology ( J:3906 )

• 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

abnormal humerus morphology ( J:3906 )

• humerus is short with irregular metaphyseal borders and poor corticomedullary demarcation

bowed humerus ( J:3906 )

short humerus ( J:3906 )

• 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

bowed radius ( J:3906 )

• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaft

• some surviving mice exhibit bowed radii

abnormal olecranon morphology ( J:3906 )

• ulna is characterized by a long zone of increased ossification corresponding to the olecranon

bowed ulna ( J:3906 )

• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaf

• some surviving mice exhibit bowed ulnae

short ulna ( J:3906 )

• 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

abnormal femur morphology ( J:3906 )

• 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

short femur ( J:3906 )

• 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

abnormal fibula morphology ( J:3906 )

• fibula is the least affected of the long bones, showing little bowing, crumbling or irregular ossification centers but is underossified

abnormal tibia morphology ( J:3906 )

• 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

bowed tibia ( J:3906 )

• surviving mutants show deformed tibiae, with variable degree of bowing

skeleton

abnormal alveolar process morphology ( J:100158 )

• defective alveolar bone mineralization

abnormal dentin development ( J:100158 )

• delayed formation of dentin in the incisor

abnormal limb bone morphology ( J:3906 )

• 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

abnormal long bone morphology ( J:3906 , J:6711 , J:100158 )

• 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)

abnormal humerus morphology ( J:3906 )

• humerus is short with irregular metaphyseal borders and poor corticomedullary demarcation

bowed humerus ( J:3906 )

bowed radius ( J:3906 )

• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaft

• some surviving mice exhibit bowed radii

abnormal olecranon morphology ( J:3906 )

• ulna is characterized by a long zone of increased ossification corresponding to the olecranon

bowed ulna ( J:3906 )

• severe bowing of the radius and ulna is seen at birth, approaching right angles and occuring mid-shaf

• some surviving mice exhibit bowed ulnae

abnormal femur morphology ( J:3906 )

• 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

abnormal fibula morphology ( J:3906 )

• fibula is the least affected of the long bones, showing little bowing, crumbling or irregular ossification centers but is underossified

abnormal tibia morphology ( J:3906 )

• 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

bowed tibia ( J:3906 )

• surviving mutants show deformed tibiae, with variable degree of bowing

abnormal clavicle morphology ( J:3906 )

• clavicle is frequently bowed at the sternal end

abnormal long bone metaphysis morphology ( J:3906 )

• surviving mutants show a broad tibial metaphysis at P1-P15

• humerus exhibits an irregular metaphysis border

• bones show fewer trabeculae within the metaphysis

decreased length of long bones ( J:6711 )

• bones are also curved

short humerus ( J:3906 )

• 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

short ulna ( J:3906 )

• 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

short femur ( J:3906 )

• 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

abnormal scapula morphology ( J:3906 )

• scapulae are always bowed

abnormal ischium morphology ( J:3906 )

• the ischium is bowed at the midline

abnormal pubis morphology ( J:3906 )

• the pubis is bowed at the midline

abnormal rib morphology ( J:3906 )

• 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

rib fractures ( J:100158 )

• multiple fractures of ribs at birth

short ribs ( J:3906 )

decreased bone mineral density ( J:3906 )

• from P1-P15, scapula appears normal in shape but is osteopenic

• 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

abnormal osteoblast morphology ( J:3906 )

• osteoblasts exhibit dilated rough endoplastic reticulum and the cisternae are more densely packed with particulate matter

abnormal periosteum morphology ( J:3906 )

• the layers of the perichondrium/periosteum are more widely separated in in neonates than controls

decreased bone trabecula number ( J:3906 )

• bones show fewer trabeculae within the metaphysis and the collar is thickened on the inner side of the bone where bowing is present

abnormal cartilage development ( J:7673 )

• initiation and progress is normal but osteoid

abnormal perichondrium morphology ( J:3906 )

• the layers of the perichondrium/periosteum are more widely separated in in neonates than controls

abnormal epiphyseal plate morphology ( J:3906 )

• 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

increased width of hypertrophic chondrocyte zone ( J:3906 )

• 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

abnormal bone ossification ( J:3906 )

• 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 imperfecta, type IIA

• surviving mice show skeletal defects similar to osteogenesis imperfecta, type IIB or III

abnormal sternum ossification ( J:3906 )

• sternum is normal in shape but fewer sternabrae are ossified

abnormal bone mineralization ( J:7673 , J:100158 )

• 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)

delayed bone ossification ( J:3906 )

• 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

reduced fertility ( J:3906 )

• mice are poor breeders

respiratory system

respiratory distress ( J:3906 )

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

craniofacial

abnormal alveolar process morphology ( J:100158 )

• defective alveolar bone mineralization

abnormal dentin development ( J:100158 )

• delayed formation of dentin in the incisor

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta		DOID:12347	OMIM:PS166200	J:100158
osteogenesis imperfecta type 2		DOID:0110341	OMIM:166210	J:3906
osteogenesis imperfecta type 3		DOID:0110339	OMIM:259420	J:3906