Phenotypes associated with this allele

• Allele Symbol: Tg(Col2a1-cre)#Amc
• Allele Name: transgene insertion, Andrew P McMahon
• Allele ID: MGI:4840368
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Adgrg6^tm1Arte/Adgrg6^tm1Arte Tg(Col2a1-cre)#Amc/0	involves: 129S5/SvEvBrd	MGI:7266813
cn2	Zfp521^tm1Ngc/Zfp521^tm1Ngc Tg(Col2a1-cre)#Amc/0 Tg(Col2a1-PTHR1*H223R)AHju/0	involves: C57BL/6	MGI:5294939
cn3	Prmt5^tm2c(EUCOMM)Wtsi/Prmt5^tm2c(EUCOMM)Wtsi Tg(Col2a1-cre)#Amc/0	involves: C57BL/6N	MGI:7277815
cn4	Zfp521^tm1Ngc/Zfp521^tm1Ngc Tg(Col2a1-cre)#Amc/0	Not Specified	MGI:4840376

Genotype
MGI:7266813

cn1

• Allelic Composition: Adgrg6^tm1Arte/Adgrg6^tm1Arte; Tg(Col2a1-cre)#Amc/0
• Genetic Background: involves: 129S5/SvEvBrd

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

cellular

increased chondrocyte apoptosis ( J:224002 )

• increase in apoptosis in chondrocytes in the costal cartilages of the ribs and vertebrae

• in the intervertebral region increased apoptosis is seen in all chondrocytes including within the hypertrophic zone, annulus fibrosis and within the nucleus pulposus

skeleton

skeleton phenotype ( J:224002 , J:313834 )

N • no changes in trabecular bone of the vertebrae and no overt changes in the craniofacial or appendicular skeleton (J:224002)

N • no apparent defects in the size or patterning of the vertebrae, growth plates, or intervertebral disk tissues at P20 (J:313834)

increased chondrocyte apoptosis ( J:224002 )

• increase in apoptosis in chondrocytes in the costal cartilages of the ribs and vertebrae

• in the intervertebral region increased apoptosis is seen in all chondrocytes including within the hypertrophic zone, annulus fibrosis and within the nucleus pulposus

abnormal sternum morphology ( J:224002 )

• dorsal-ward pectus excavatum-like deflections in the sternum in some mice

abnormal intervertebral disk morphology ( J:224002 , J:313834 )

• at P0 and P20 acellular clefts are seen at the midline in the region of the annulus fibrosis (J:224002)

• wedging of intervertebral disks is seen close to the apex of the curvature (J:313834)

• more vertical alignment of the annulus fibrosis lamellae along the convex side with flatter lamellae and an elongated inner annulus fibrosus at the concave side (J:313834)

• at P120 but not at P20 endplate and growth plate tissues appeared thinner (J:313834)

• however, disks proximal or distal to the curvature appear normal (J:313834)

abnormal nucleus pulposus morphology ( J:313834 )

• shifted towards the convexity of the curve and this is more pronounced in older scoliotic mice

• large vacuolated cells are shifted towards the the convex side and smaller non-vacuolated cells are in the middle and concave side, unlike in controls where these cells are evenly distributed

scoliosis ( J:224002 , J:313834 )

• thoracic scoliosis in a significant fraction of mice (J:224002)

• postnatal onset of spine curvature beginning at P20 (J:313834)

• scoliosis is progressive in some mice (J:313834)

• scoliosis is seen in 60% of mice at P20, P40 and P120 (J:313834)

• apex of curvature is centered at thoracic vertebrae (T)8 and T9 with a Cobb angle ranging from 11 to 46 degrees (J:313834)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic scoliosis		DOID:0060250		J:224002

Genotype
MGI:5294939

cn2

• Allelic Composition: Zfp521^tm1Ngc/Zfp521^tm1Ngc; Tg(Col2a1-cre)#Amc/0; Tg(Col2a1-PTHR1*H223R)AHju/0
• Genetic Background: involves: C57BL/6

skeleton

skeleton phenotype ( J:175572 )

N • mice exhibit normal bone length

N • tibial growth plate of mutants is similar to wild-type, indicating rescue of the chondrocyte differentiation delay seen in single Tg(Col2a1-PTHR1*H223R)AHju/0 mice and improvement in endochondral bone formation

Genotype
MGI:7277815

cn3

• Allelic Composition: Prmt5^{tm2c(EUCOMM)Wtsi}/Prmt5^{tm2c(EUCOMM)Wtsi}; Tg(Col2a1-cre)#Amc/0
• Genetic Background: involves: C57BL/6N

mortality/aging

preweaning lethality, complete penetrance ( J:283043 )

• most die before P10 with none surviving to P16

growth/size/body

decreased body size ( J:283043 )

• of 4 mice that survived to P10, 2 are much smaller than littermate controls

skeleton

abnormal intervertebral disk morphology ( J:283043 )

• at P1 an increase in midline clefts in the endplate are seen

• at P10, chondrocytes in the endplate appear larger and the surrounding matrix is more intensely stained with Alcian Blue

• the inner and outer layers of the annulus fibrosus stain more intensely with Alcian Blue

abnormal intervertebral disk development ( J:283043 )

• expression analysis indicates abnormal differentiation of cartilaginous tissues

scoliosis ( J:283043 )

• thoracic scoliosis at P10 with an average Cobb angle of 30 +/- 4 degrees

abnormal vertebrae morphology ( J:283043 )

• some mild wedging of the vertebra at the apex of the curvature

• severe decrease in trabecular bone formation in the T6 vertebra

• delay in the formation of the endochondral ossification in the vertebral bodies at P1 and an increase in midline clefts in the vertebral growth plate

• at P10, there is an increased number of cell layers in the hypertrophic zone of the vertebral growth plate and a minor increase in the number of cells or cell layers in the proliferative/prehypertrophic zone of the growth plate

abnormal vertebral body development ( J:283043 )

• expression analysis indicates abnormal differentiation of cartilaginous tissues in the growth plate of the spine

small vertebrae ( J:283043 )

• overall smaller vertebrae

decreased trabecular bone volume ( J:283043 )

• in the T6 vertebra

abnormal chondrocyte morphology ( J:283043 )

• general disorganization of chondrocytes in the vertebrae

• at P10, chondrocytes in the intervertebral disk endplate appear larger and the surrounding matrix is more intensely stained with Alcian Blue

decreased bone mineralization ( J:283043 )

• lateral X-rays show reduced signal attenuation in the distal ribs indicative of reduced mineralized bone

abnormal endochondral bone ossification ( J:283043 )

• impaired in the thoracic vertebral bodies at P1 and P10

delayed endochondral bone ossification ( J:283043 )

• delay in the formation of the endochondral ossification in the vertebral bodies at P1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic scoliosis		DOID:0060250		J:283043

Genotype
MGI:4840376

cn4

• Allelic Composition: Zfp521^tm1Ngc/Zfp521^tm1Ngc; Tg(Col2a1-cre)#Amc/0
• Genetic Background: Not Specified

skeleton

abnormal long bone epiphyseal plate morphology ( J:166058 )

• the transition to the hypetrophic zone is closer to the epiphysis with fewer chondrocytes of increased cellular height and reduced matrix compared with wild-type mice

abnormal long bone epiphyseal plate proliferative zone ( J:166058 )

• reduced

decreased width of hypertrophic chondrocyte zone ( J:166058 )

decreased long bone epiphyseal plate size ( J:166058 )

• with a reduction in the number of cell columns and cells per column

decreased length of long bones ( J:166058 , J:175572 )

small thoracic cage ( J:166058 )

small vertebrae ( J:166058 )

abnormal bone structure ( J:166058 )

• bones formed by endochondral ossification are smaller than in wild-type mice

• however, craniofacial structures that develop by intramembranous ossification and the cranium base synchondroses are normal

abnormal bone mineralization ( J:166058 )

• extracellular matrix mineralization is premature compared to in wild-type mice

abnormal chondrocyte physiology ( J:166058 , J:175572 )

• growth plate chondrocytes exhibit reduced proliferation compared to in wild-type mice (J:166058)

• chondrocyte progression to hypertrophy is slowed compared to in wild-type mice (J:166058)

• chondrocyte apoptosis is increased compared to in wild-type mice (J:166058)

growth/size/body

proportional dwarf ( J:166058 )

postnatal growth retardation ( J:166058 , J:175572 )

• beginning at 1 to 2 weeks of age and persisting through 8 and 12 weeks (J:166058)