Phenotypes associated with this allele

• Allele Symbol: Col2a1^tm1Prc
• Allele Name: targeted mutation 1, Darwin J Prockop
• Allele ID: MGI:2152978
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Col2a1^tm1Prc/Col2a1^tm1Prc	involves: 129	MGI:3590207
hm2	Col2a1^tm1Prc/Col2a1^tm1Prc	involves: 129/Sv * C57BL/6	MGI:2677039
ht3	Col2a1^tm1Prc/Col2a1^+	involves: 129/Sv * C57BL/6	MGI:2677040
cx4	Col2a1^tm1Prc/Col2a1^+ Col9a1^tm1Jae/Col9a1^tm1Jae	involves: 129/Sv * 129S2/SvPas	MGI:3699109

Genotype
MGI:3590207

hm1

• Allelic Composition: Col2a1^tm1Prc/Col2a1^tm1Prc
• Genetic Background: involves: 129

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

growth/size/body

short nasal bone ( J:117910 )

decreased embryo size ( J:84739 )

• shorter trunk

abnormal chest morphology ( J:84739 , J:117910 )

• thorax is narrowed (J:84739)

decreased body length ( J:117910 )

disproportionate dwarf ( J:84739 , J:117910 )

skeleton

short facial bone ( J:117910 )

• facial bones are shortened

short mandible ( J:117910 )

short nasal bone ( J:117910 )

domed cranium ( J:117910 )

• chondrocranium is shortened leading to a dome shaped skull

• however, membranous bones in the head develop normally

abnormal long bone morphology ( J:117910 )

abnormal long bone metaphysis morphology ( J:84739 , J:117910 )

• greatly shortened (J:84739)

decreased length of long bones ( J:84739 , J:117910 )

• shorter long bones (J:84739)

abnormal rib morphology ( J:84739 , J:117910 )

• size and shape of ribs are abnormal (J:84739)

abnormal vertebral body morphology ( J:117910 )

• vertebral body cartilage is structurally disorganized and lacks ossification centers

enlarged vertebral body ( J:84739 , J:117910 )

• vertebral bodies are increased in size and have an abnormal shape (J:84739)

abnormal trabecular bone morphology ( J:117910 )

• trabecular bones are oriented transversely instead of perpendicular to the direction of longitudinal growth

abnormal cartilage morphology ( J:117910 )

• weak cartilage

• lacunar organization within cartilage is missing

• proteoglycan content is decreased throughout cartilage

absent intervertebral disk ( J:84739 , J:117910 )

abnormal articular cartilage morphology ( J:117910 )

• the forming articular surface of cartilage is irregular and covered with several fibrous-like cell layers

abnormal skeleton development ( J:84739 )

abnormal long bone epiphyseal plate morphology ( J:117910 )

• cartilage lacks growth plates although cells resembling hypertrophic chondrocytes are seen adjacent to the ossification zone

abnormal long bone hypertrophic chondrocyte zone ( J:84739 , J:117910 )

• matrix in the hypertrophic-like zone is poorly mineralized (J:117910)

disorganized long bone epiphyseal plate ( J:84739 )

• growth plates are disorganized

increased long bone epiphyseal plate size ( J:84739 )

• epiphyseal cartilages of femur and tibia are enlarged and frequently contain holes

abnormal long bone epiphysis morphology ( J:117910 )

• epiphyseal cartilages of femur and tibia are enlarged and frequently contain holes

abnormal cartilage development ( J:84739 )

• completely lack a well-organized collagen fibrillar network in all zones of cartilage

chondrodystrophy ( J:84739 )

abnormal endochondral bone ossification ( J:84739 , J:117910 )

• all bones formed by endochondral bone ossification are malformed (J:84739)

embryo

decreased embryo size ( J:84739 )

• shorter trunk

persistence of notochord tissue ( J:84739 )

• the rod-like notochord remains unchanged in late development

craniofacial

short facial bone ( J:117910 )

• facial bones are shortened

short mandible ( J:117910 )

short nasal bone ( J:117910 )

domed cranium ( J:117910 )

• chondrocranium is shortened leading to a dome shaped skull

• however, membranous bones in the head develop normally

respiratory system

short nasal bone ( J:117910 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondrogenesis type II		DOID:0080056	OMIM:200610	J:117910

Genotype
MGI:2677039

hm2

• Allelic Composition: Col2a1^tm1Prc/Col2a1^tm1Prc
• Genetic Background: involves: 129/Sv * C57BL/6

Abnormal intervertebral disc development in Col2a1^tm1Prc/Col2a1^tm1Prc mice

mortality/aging

perinatal lethality, complete penetrance ( J:30041 )

• all dead at birth

cardiovascular system

abnormal heart valve morphology ( J:30041 )

• short

increased renal plasma flow rate ( J:30041 )

• kidney hyperemia

kidney hemorrhage ( J:30041 )

craniofacial

small cranium ( J:30041 )

short facial bone ( J:30041 )

• truncated facial bones

absent palatal shelf ( J:30041 )

prominent forehead ( J:30041 )

• bulged foreheads

cleft palate ( J:30041 )

• all mice lacked a palate with no evidence of palatal shelves

short snout ( J:30041 )

embryo

persistence of notochord tissue ( J:51376 )

• not removed during embryonic development, persisted until birth

growth/size/body

absent palatal shelf ( J:30041 )

prominent forehead ( J:30041 )

• bulged foreheads

cleft palate ( J:30041 )

• all mice lacked a palate with no evidence of palatal shelves

short snout ( J:30041 )

decreased body size ( J:30041 )

• 25% smaller than wild-type littermates

immune system

immune system phenotype ( J:30041 )

N • normal thymus histology

limbs/digits/tail

decreased autopod size ( J:30041 )

• small hands and feet, with short bones

abnormal limb bone morphology ( J:30041 )

short limbs ( J:30041 )

• compared to wild-type littermates

liver/biliary system

liver/biliary system phenotype ( J:30041 )

N • normal liver histology

renal/urinary system

increased renal plasma flow rate ( J:30041 )

• kidney hyperemia

kidney hemorrhage ( J:30041 )

respiratory system

abnormal pulmonary alveolus morphology ( J:30041 )

• closed

respiratory distress ( J:30041 )

skeleton

small cranium ( J:30041 )

short facial bone ( J:30041 )

• truncated facial bones

abnormal limb bone morphology ( J:30041 )

abnormal long bone epiphysis morphology ( J:30041 )

• absent

decreased length of long bones ( J:30041 )

• shortened long bones

short ribs ( J:30041 )

• shortened ribs

absent intervertebral disk ( J:51376 )

• failed to develop

abnormal vertebral arch morphology ( J:30041 )

• rudimentary and unclosed

abnormal bone marrow cavity morphology ( J:30041 )

• cavities evident in long bones, but no marrow present

decreased bone mineral density ( J:30041 )

• poor mineralization of the sternum, dorsal laminae, some, but not all, vertebrae in tail and the middle and distal phalanges

abnormal cartilage development ( J:30041 , J:51376 )

• evident at E14.5, failure of cartilage to enter growth plates and endochondral bone (J:51376)

abnormal chondrocyte morphology ( J:30041 , J:51376 )

• almost completely disorganized columnar array (J:30041)

• disorganized in vertebrae at E14.5 (J:51376)

vision/eye

vision/eye phenotype ( J:30041 )

N • normal eye histology

digestive/alimentary system

absent palatal shelf ( J:30041 )

cleft palate ( J:30041 )

• all mice lacked a palate with no evidence of palatal shelves

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spondyloepiphyseal dysplasia congenita		DOID:14789	OMIM:183900	J:30041

Genotype
MGI:2677040

ht3

• Allelic Composition: Col2a1^tm1Prc/Col2a1⁺
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:30041 )

• those with cleft palate, 5 of 120, were dead at birth or shortly thereafter

craniofacial

prominent forehead ( J:30041 )

• slightly bulged foreheads

cleft palate ( J:30041 )

• incomplete penetrance, 5 of 120

short snout ( J:30041 )

• compared to wild-type littermates

growth/size/body

prominent forehead ( J:30041 )

• slightly bulged foreheads

cleft palate ( J:30041 )

• incomplete penetrance, 5 of 120

short snout ( J:30041 )

• compared to wild-type littermates

decreased body size ( J:30041 )

• smaller than wild-type littermates at 19 days after birth

decreased fetal size ( J:30041 )

• smaller than wildtype at 15 days pc

limbs/digits/tail

short limbs ( J:30041 )

• compared to wild-type littermates

skeleton

abnormal chondrocyte morphology ( J:30041 )

• disorganized columnar array

abnormal skeleton development ( J:30041 )

• minor changes in gross development of skeleton and soft tissues, however normal extent of mineralization

abnormal cartilage development ( J:30041 )

vision/eye

vision/eye phenotype ( J:144313 )

N • despite eye abnormalities, no increase in retinal detachment is observed

abnormal anterior eye segment morphology ( J:144313 )

• the anterior eye segment exhibits decreased folding in the ciliary process with changes in the stromal extracellular matrix and vacuolization compared to in wild-type eyes

abnormal ciliary process morphology ( J:144313 )

• typical folding of ciliary processes is reduced

abnormal lens morphology ( J:144313 )

• the subcapsular extracellular matrix is abnormal

abnormal posterior eye segment morphology ( J:144313 )

• hyaluronic acid staining in the choroid is decreased in intensity compared to in wild-type mice

digestive/alimentary system

cleft palate ( J:30041 )

• incomplete penetrance, 5 of 120

homeostasis/metabolism

decreased hyaluronic acid level ( J:144313 )

• hyaluronic acid staining in the choroid is decreased in intensity compared to in wild-type mice

Genotype
MGI:3699109

cx4

• Allelic Composition: Col2a1^tm1Prc/Col2a1⁺; Col9a1^tm1Jae/Col9a1^tm1Jae
• Genetic Background: involves: 129/Sv * 129S2/SvPas

immune system

osteoarthritis ( J:117910 )

• develop osteoarthritis-like degenerative changes in knee joints to similar extent as in single Col9a1 homozygotes; show no difference in the onset of osteoarthritis between the double mutants and the single Col9a1 homozygotes

skeleton

osteoarthritis ( J:117910 )

• develop osteoarthritis-like degenerative changes in knee joints to similar extent as in single Col9a1 homozygotes; show no difference in the onset of osteoarthritis between the double mutants and the single Col9a1 homozygotes