Phenotypes associated with this allele

• Allele Symbol: Tg(Col2a1-cre)1Bhr
• Allele Name: transgene insertion 1, Richard R Behringer
• Allele ID: MGI:2176070
• Summary: 56 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Fermt2^tm1.1Gxo/Fermt2^tm1.1Gxo Tg(Col2a1-cre)1Bhr/0	B6.Cg-Fermt2^tm1.1Gxo Tg(Col2a1-cre)1Bhr	MGI:5792566
cn2	n-TUtca2^tm1Dhat/n-TUtca2^tm1Dhat Tg(Col2a1-cre)1Bhr/0	B6.Cg-n-TUtca2^tm1Dhat Tg(Col2a1-cre)1Bhr	MGI:4360984
cn3	Sox9^tm3.1Tlu/Sox9^+ Tg(Col2a1-cre)1Bhr/0	either: (involves: 129S4/SvJae * C57BL/6 * SJL) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL)	MGI:5560998
cn4	Sox9^tm3.1Tlu/Sox9^tm3.1Tlu Tg(Col2a1-cre)1Bhr/0	either: (involves: 129S4/SvJae * C57BL/6 * SJL) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL)	MGI:5560999
cn5	Hdac8^tm1.1Eno/Y Tg(Col2a1-cre)1Bhr/0	involves: 129 * C57BL/6 * CD-1 * SJL	MGI:3851916
cn6	Ctnnb1^tm2Kem/Ctnnb1^+ Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Tg(Col2a1-cre)1Bhr/0 Tg(tetO-Vegfa)90Ala/0	involves: 129 * C57BL/6 * FVB/N * ICR * SJL	MGI:4429127
cn7	Ntrk2^tm2Lfp/Ntrk2^tm2Lfp Tg(Col2a1-cre)1Bhr/0	involves: 129 * C57BL/6 * SJL	MGI:5532837
cn8	Reck^tm2.1Noda/Reck^tm2.2Noda Tg(Col2a1-cre)1Bhr/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL	MGI:5428659
cn9	Sox9^tm1Gsr/Sox9^tm1Gsr Tg(Col2a1-cre)1Bhr/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:3710214
cn10	Sox9^tm1Gsr/Sox9^+ Tg(Col2a1-cre)1Bhr/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:3710216
cn11	Ift88^tm1Bky/Ift88^tm1Bky Tg(Col2a1-cre)1Bhr/?	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:3710958
cn12	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Tg(Col2a1-cre)1Bhr/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3045412
cn13	Gt(ROSA)26Sor^tm5(ACTB-tTA)Luo/Gt(ROSA)26Sor^+ Tg(Col2a1-cre)1Bhr/0 Tg(tetO/CMV-Col2a1*R992C,-GFP)#Afe/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL	MGI:5643754
cn14	Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Tg(Col2a1-cre)1Bhr/0 Tg(tetO-Vegfa)90Ala/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N * SJL	MGI:4429125
cn15	Gt(ROSA)26Sor^tm1(Vegfa*)Jhai/Gt(ROSA)26Sor^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * ICR * SJL	MGI:4429123
cn16	Gt(ROSA)26Sor^tm1(Vegfa*)Jhai/Gt(ROSA)26Sor^+ Kdr^tm1Wag/Kdr^tm1Wag Tg(Col2a1-cre)1Bhr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * ICR * SJL	MGI:4429126
cn17	Vdr^tm1Gcm/Vdr^tm1Gcm Tg(Col2a1-cre)1Bhr/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3813812
cn18	Ext1^tm1Vcs/Ext1^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4437602
cn19	Kif3a^tm2Gsn/Kif3a^tm2Gsn Tg(Col2a1-cre)1Bhr/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3710959
cn20	Mapk8^tm1Rjd/Mapk8^tm1Rjd Mapk9^tm1Flv/Mapk9^tm1Flv Tg(Col2a1-cre)1Bhr/0	involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL	MGI:7279112
cn21	Fgfr3^tm2Llm/Fgfr3^+ Tg(Col2a1-cre)1Bhr/?	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:5426513
cn22	Sox9^tm4.1Tlu/Sox9^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL	MGI:5293349
cn23	Sox9^tm4.1Tlu/Sox9^tm4.1Tlu Tg(Col2a1-cre)1Bhr/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL	MGI:5293350
cn24	Casr^tm1Wch/Casr^tm1Wch Tg(Col2a1-cre)1Bhr/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5306893
cn25	Amer1^tm1.1Nbar/Y Tg(Col2a1-cre)1Bhr/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5086010
cn26	Dot1l^tm1c(KOMP)Wtsi/Dot1l^tm1c(KOMP)Wtsi Tg(Col2a1-cre)1Bhr/0	involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6N * SJL	MGI:6284806
cn27	Ctnnb1^tm1Yy/Ctnnb1^tm1Yy Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6	MGI:3056288
cn28	Serpinh1^tm2Kzn/Serpinh1^tm2Kzn Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL	MGI:5505276
cn29	Fgfr3^tm4Cxd/Fgfr3^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6 * NIH Black Swiss * SJL	MGI:3640323
cn30	Ctnnb1^tm1Yy/Ctnnb1^tm1.1Yy Ptch1^tm1Yy/Ptch1^tm1.1Yy Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3687747
cn31	Ctnnb1^tm1Yy/Ctnnb1^tm1.1Yy Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3687748
cn32	Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Col2a1-cre)1Bhr/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3846228
cn33	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col2a1-cre)1Bhr/?	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3785772
cn34	Sox9^tm2Crm/Sox9^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:2451169
cn35	Gt(ROSA)26Sor^tm1(Wnt4)Bhr/Gt(ROSA)26Sor^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3769501
cn36	Sox9^tm2Crm/Sox9^tm2Crm Tg(Col2a1-cre)1Bhr/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:2451170
cn37	Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Col2a1-cre)1Bhr/?	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3785771
cn38	Mef2c^tm1Eno/Mef2c^tm2Eno Tg(Col2a1-cre)1Bhr/0	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3719016
cn39	Ndrg2^tm1Xzg/Ndrg2^tm1Xzg Tg(Col2a1-cre)1Bhr/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:5441473
cn40	Mef2c^tm2Eno/Mef2c^tm2Eno Mef2d^tm1Eno/Mef2d^tm1Eno Tg(Col2a1-cre)1Bhr/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:3719017
cn41	Sox5^tm1Vlf/Sox5^tm1Vlf Sox6^tm1Vlf/Sox6^tm2.1Vlf Tg(Col2a1-cre)1Bhr/0	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3641207
cn42	Trip11^tm1.1Psmi/Trip11^tm1.2Psmi Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/? Tg(Col2a1-cre)1Bhr/?	involves: 129/Sv * C57BL/6 * SJL/J	MGI:6154156
cn43	Ctnnb1^tm1Mmt/Ctnnb1^+ Tg(Col2a1-cre)1Bhr/0	involves: 129X1/SvJ	MGI:3045411
cn44	Smad1^tm1Abr/Smad1^tm1.1Abr Tg(Col2a1-cre)1Bhr/0	involves: BALB/cJ * C57 * C57BL/6 * SJL	MGI:5009239
cn45	Csgalnact1^tm1Nari/Csgalnact1^tm1Nari Csgalnact2^tm1.1Staka/Csgalnact2^tm1.1Staka Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:6117390
cn46	Tg(CAG-cat,-Twist1)1Dbsp/0 Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * FVB * SJL	MGI:5487798
cn47	Gpc6^tm2c(EUCOMM)Wtsi/Gpc6^tm2c(EUCOMM)Wtsi Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6N * SJL	MGI:6098732
cn48	Runx3^tm3Yg/Runx3^tm3Yg Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:5689564
cn49	Idh1^tm3Mak/Idh1^+ Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:5635889
cn50	Runx2^tm1Javed/Runx2^tm1Javed Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:5582463
cn51	Mapk14^tm1.2Otsu/Mapk14^tm1.2Otsu Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:5532835
cn52	Adamts17^tm1.1Taks/Adamts17^tm1.1Taks Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:6466736
cn53	Ptch1^tm1Yy/Ptch1^tm1.1Yy Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:3687745
cn54	Tg(CAG-mRFP1,-SOX9,-EGFP)1Haak/0 Tg(Col2a1-cre)1Bhr/0	involves: C57BL/6 * SJL	MGI:5297172
cn55	Sp7^tm1Rnis/Sp7^tm1Rnis Tg(Col2a1-cre)1Bhr/0	involves: C57BL * C57BL/6 * CBA/JNCrlj * SJL	MGI:5466672
tg56	Tg(Col2a1-cre)1Bhr/Tg(Col2a1-cre)1Bhr	involves: C57BL/6 * SJL	MGI:5532836

Genotype
MGI:5792566

cn1

• Allelic Composition: Fermt2^tm1.1Gxo/Fermt2^tm1.1Gxo; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: B6.Cg-Fermt2^tm1.1Gxo Tg(Col2a1-cre)1Bhr

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

mortality/aging

premature death ( J:224370 )

• mice die within 1 month of birth because of respiratory distress

growth/size/body

decreased body size ( J:224370 )

• severe dwarfism at P20

postnatal growth retardation ( J:224370 )

• all mice develop rapid growth retardation after birth

respiratory system

respiratory distress ( J:224370 )

• respiratory distress probably associated with compression of cervical and thoracic vertebrae as a result of kyphosis

limbs/digits/tail

decreased femur compact bone thickness ( J:224370 )

• significant reduction in femur cortical bone thickness at P30

short limbs ( J:224370 )

• P0 forelimbs and hindlimbs are shorter than normal

skeleton

skeleton phenotype ( J:224370 )

N • mice do not exhibit any marked abnormalities in the skull vault and clavicle, suggesting normal intramembraneous ossification

abnormal skeleton morphology ( J:224370 )

• reduced skeleton size at P0 and P20

decreased femur compact bone thickness ( J:224370 )

• significant reduction in femur cortical bone thickness at P30

abnormal long bone epiphyseal plate morphology ( J:224370 )

• at P0, representative images of proliferative and hypertrophic zone chondrocytes show disrupted column formation in humeral sections

decreased length of long bones ( J:224370 )

• significant reduction in the length of all long bones (femur, tibia, humerus, radius and ulna) and their respective bony portions at P0

small thoracic cage ( J:224370 )

• P0 ribcage is smaller than normal

kyphosis ( J:224370 )

• ~80% of mice develop progressive kyphosis

• severe kyphosis at P20

vertebral compression ( J:224370 )

• compression of cervical and thoracic vertebrae resulting from kyphosis

small vertebrae ( J:224370 )

• vertebrae are shorter than normal

decreased bone mineral density ( J:224370 )

decreased trabecular bone volume ( J:224370 )

• dramatic reduction in femur trabecular bone volume/tissue volume (BV/TV) at P30

delayed endochondral bone ossification ( J:224370 )

• Alcian blue stain of P17 and P30 tibial sections indicates delayed formation of the secondary ossification center and reduced subchondral bone

Genotype
MGI:4360984

cn2

• Allelic Composition: n-TUtca2^tm1Dhat/n-TUtca2^tm1Dhat; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: B6.Cg-n-TUtca2^tm1Dhat Tg(Col2a1-cre)1Bhr

Small size, hypomorphic ears and shortened snout in n-TUtca2^tm1Dhat/n-TUtca2^tm1Dhat Tg(Col2a1-cre)1Bhr/0 mice

mortality/aging

premature death ( J:152152 )

• at 4 to 5 weeks with rib cage indrawing suggestive of inspiratory respiratory distress

skeleton

abnormal skeleton morphology ( J:152152 )

• small skeleton

• however, the width of the radiolucent gap corresponding to the tibia epiphyseal growth plates is normal

abnormal cranium morphology ( J:152152 )

• rounding of the cranium

small cranium ( J:152152 )

abnormal neurocranium morphology ( J:152152 )

• rounding of the calvaria unlike in Trnau1^tm1Dhat homozygous control mice

abnormal frontal bone morphology ( J:152152 )

• frontal bones are more porous than in Trnau1^tm1Dhat homozygous control mice

frontal bossing ( J:152152 )

abnormal jaw morphology ( J:152152 )

• narrowing of the jaw unlike in Trnau1^tm1Dhat homozygous control mice

decreased length of long bones ( J:152152 )

abnormal vertebrae morphology ( J:152152 )

• the space between vertebral bodies is smaller than in Trnau1^tm1Dhat homozygous control mice

abnormal lumbar vertebrae morphology ( J:152152 )

• lumbar vertebrae are small with irregular outlines and have uneven ossification unlike in Trnau1^tm1Dhat homozygous control mice

abnormal cartilage morphology ( J:152152 )

• mice exhibit areas of chondronecrosis in the articular cartilage of the knees unlike in Trnau1^tm1Dhat homozygous control mice

• chondronecrosis is present in the femoral condylar and tibial plateau articular cartilage, auricular, and trachea

abnormal tracheal cartilage morphology ( J:152152 )

• mice exhibit hypoplasia and chondronecrosis with scattered apoptotic cells in the tracheal cartilage unlike in Trnau1^tm1Dhat homozygous control mice

• tracheal rings are reduced in size and chondrocyte content compared to in Trnau1^tm1Dhat homozygous control mice

abnormal long bone epiphyseal plate morphology ( J:152152 )

• the primary spongiosa is disorganized compared to in Trnau1^tm1Dhat homozygous control mice

abnormal long bone epiphyseal plate proliferative zone ( J:152152 )

• increased

increased width of hypertrophic chondrocyte zone ( J:152152 )

increased long bone epiphyseal plate size ( J:152152 )

• the tibia growth plate width is increased 45% compared to in Trnau1^tm1Dhat homozygous control mice

abnormal skeleton physiology ( J:152152 )

• proliferation of cells within the tibia growth plate is decrease while apoptosis is moderately increased compared to in Trnau1^tm1Dhat homozygous control mice

tracheomalacia ( J:152152 )

• mice exhibit tracheomalacia

abnormal bone mineralization ( J:152152 )

• long bone mineralization is impaired compared to in Trnau1^tm1Dhat homozygous control mice

delayed bone ossification ( J:152152 )

• lumbar vertebrae have uneven ossification unlike in Trnau1^tm1Dhat homozygous control mice

growth/size/body

frontal bossing ( J:152152 )

short snout ( J:152152 )

outer ear hypoplasia ( J:152152 )

• auricle hypoplasia

microcephaly ( J:152152 )

• decreased head size with frontal bossing

decreased body size ( J:152152 )

• 1 week after birth

decreased body length ( J:152152 )

• at 3.5 to 4 weeks but not at P1

postnatal growth retardation ( J:152152 )

hearing/vestibular/ear

outer ear hypoplasia ( J:152152 )

• auricle hypoplasia

respiratory system

abnormal tracheal cartilage morphology ( J:152152 )

• mice exhibit hypoplasia and chondronecrosis with scattered apoptotic cells in the tracheal cartilage unlike in Trnau1^tm1Dhat homozygous control mice

• tracheal rings are reduced in size and chondrocyte content compared to in Trnau1^tm1Dhat homozygous control mice

trachea stenosis ( J:152152 )

• mice exhibit a narrowing of the airway lumen unlike in Trnau1^tm1Dhat homozygous control mice

tracheomalacia ( J:152152 )

• mice exhibit tracheomalacia

craniofacial

abnormal cranium morphology ( J:152152 )

• rounding of the cranium

small cranium ( J:152152 )

abnormal neurocranium morphology ( J:152152 )

• rounding of the calvaria unlike in Trnau1^tm1Dhat homozygous control mice

abnormal frontal bone morphology ( J:152152 )

• frontal bones are more porous than in Trnau1^tm1Dhat homozygous control mice

frontal bossing ( J:152152 )

abnormal jaw morphology ( J:152152 )

• narrowing of the jaw unlike in Trnau1^tm1Dhat homozygous control mice

abnormal craniofacial development ( J:152152 )

• chondrocranial growth is impaired compared to in Trnau1^tm1Dhat homozygous control mice

short snout ( J:152152 )

outer ear hypoplasia ( J:152152 )

• auricle hypoplasia

limbs/digits/tail

abnormal limb morphology ( J:152152 )

• mice exhibit small knees compared with Trnau1^tm1Dhat homozygous control mice

short limbs ( J:152152 )

short tail ( J:152152 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
connective tissue disease		DOID:65		J:152152

Genotype
MGI:5560998

cn3

• Allelic Composition: Sox9^tm3.1Tlu/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: either: (involves: 129S4/SvJae * C57BL/6 * SJL) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL)

behavior/neurological

hunched posture ( J:207801 )

growth/size/body

decreased body height ( J:207801 )

Genotype
MGI:5560999

cn4

• Allelic Composition: Sox9^tm3.1Tlu/Sox9^tm3.1Tlu; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: either: (involves: 129S4/SvJae * C57BL/6 * SJL) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL)

skeleton

scapular bone hypoplasia ( J:207801 )

abnormal cartilage development ( J:207801 )

• loss of cartilaginous tissues

premature bone ossification ( J:207801 )

• in the axial and appendicular skeleton

limbs/digits/tail

abnormal forelimb stylopod morphology ( J:207801 )

• foreshortened

abnormal forelimb zeugopod morphology ( J:207801 )

• foreshortened

Genotype
MGI:3851916

cn5

• Allelic Composition: Hdac8^tm1.1Eno/Y; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * SJL

normal phenotype

no abnormal phenotype detected ( J:150709 )

♂ • no abnormal phenotype is detected in skull development

Genotype
MGI:4429127

cn6

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1⁺; Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Tg(Col2a1-cre)1Bhr/0; Tg(tetO-Vegfa)90Ala/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N * ICR * SJL

neoplasm

increased hemangioma incidence ( J:156474 )

• local bone and marrow tissue in doxycycline-treat mice are replaced with massively enlarged vascular structures (hemangiomas) unlike in wild-type mice

skeleton

skeleton phenotype ( J:156474 )

N • doxycycline-treat mice exhibit normal bone density, osteoclastic bone remodeling, and bone degradation

Genotype
MGI:5532837

cn7

• Allelic Composition: Ntrk2^tm2Lfp/Ntrk2^tm2Lfp; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:204227 )

♀ • most severely dwarfed female mice do not survive beyond P3 and none of the extremely dwarfed mice survive beyond 2 weeks

growth/size/body

decreased birth body size ( J:204227 )

♀ • in some female mice

♀ • however, male mice exhibit normal size at birth

decreased body size ( J:204227 )

♀ • in female mice

decreased body weight ( J:204227 )

♀ • in female mice

♀ • however, male mice exhibit normal body weight

decreased body length ( J:204227 )

• in female and male mice

postnatal growth retardation ( J:204227 )

• at 3.5 weeks in male mice

• at 4.5 to 5 weeks in female mice

skeleton

decreased width of hypertrophic chondrocyte zone ( J:204227 )

♂ • in male mice

decreased long bone epiphyseal plate size ( J:204227 )

♂ • in male mice

kyphosis ( J:204227 )

♂ • exaggerated in male mice at 6 months

Genotype
MGI:5428659

cn8

• Allelic Composition: Reck^tm2.1Noda/Reck^tm2.2Noda; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

limbs/digits/tail

limbs/digits/tail phenotype ( J:184585 )

N • mice exhibit normal limb patterning

Genotype
MGI:3710214

cn9

• Allelic Composition: Sox9^tm1Gsr/Sox9^tm1Gsr; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

mortality/aging

perinatal lethality, complete penetrance ( J:121352 )

• die at birth

cardiovascular system

thick interventricular septum ( J:121352 )

• width of the interventricular septum is increased

abnormal heart valve morphology ( J:121352 )

• heart valve leaflets are thickened at E18.5

• abnormal organization of the stratified extracellular matrix layers within the valve leaflets

abnormal mitral valve morphology ( J:121352 )

abnormal tricuspid valve morphology ( J:121352 )

respiratory system

abnormal respiration ( J:121352 )

• respiratory defects

Genotype
MGI:3710216

cn10

• Allelic Composition: Sox9^tm1Gsr/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

cardiovascular system

abnormal heart valve morphology ( J:121352 )

• 75% of mutants, starting at 3 months of age, show mineral deposits in atrioventricular and outflow tract heart valve leaflets compared to 37.5% of controls

abnormal atrioventricular valve morphology ( J:121352 )

• the atrioventricular valve leaflet area is greater than in controls and is associated with an increase in proteoglycans at the tip of the valve leaflets

calcified mitral valve ( J:121352 )

• adult mitral valves show calcium deposits

abnormal semilunar valve morphology ( J:121352 )

• the outflow tract valve leaflet area is greater than in controls and is associated with an increase in proteoglycans at the tip of the valve leaflets

thick heart valve cusps ( J:121352 )

• from 3 months of age, heart valve leaflets are thickened

Genotype
MGI:3710958

cn11

• Allelic Composition: Ift88^tm1Bky/Ift88^tm1Bky; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

growth/size/body

disproportionate dwarf ( J:121342 )

• at P30 dawrfism is observed

• however, at P0 mice appear normal

skeleton

abnormal long bone epiphyseal plate morphology ( J:121342 )

• at P15, growth plate structure is completely abrogated with ossification centers merged and the distance from the articular surface to the trabecular bone is reduced

Genotype
MGI:3045412

cn12

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

craniofacial

abnormal craniofacial bone morphology ( J:90567 )

domed cranium ( J:90567 )

limbs/digits/tail

short limbs ( J:90567 )

skeleton

abnormal craniofacial bone morphology ( J:90567 )

domed cranium ( J:90567 )

decreased length of long bones ( J:90567 )

• endochondral bone elements all shorter

abnormal cartilage morphology ( J:90567 )

abnormal chondrocyte morphology ( J:90567 )

• chondrocyte morphology reduced about 34%

Genotype
MGI:5643754

cn13

• Allelic Composition: Gt(ROSA)26Sor^{tm5(ACTB-tTA)Luo}/Gt(ROSA)26Sor⁺; Tg(Col2a1-cre)1Bhr/0; Tg(tetO/CMV-Col2a1*R992C,-GFP)#Afe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * SJL

growth/size/body

abnormal head size ( J:216945 )

• shortened head

decreased body size ( J:216945 )

• mice are smaller at 6 months of age, with average mass reduced by 30%

• however, mice maintained in the presence of doxycycline exhibit normal skeletal phenotypes

decreased body length ( J:216945 )

• shortening of the trunk in 6 and 10 week old mice

skeleton

abnormal cranium size ( J:216945 )

• reduction in length/width ratio of the skull

increased diameter of femur ( J:216945 )

increased diameter of tibia ( J:216945 )

abnormal long bone epiphyseal plate morphology ( J:216945 )

• the extracellular content of collagen II is reduced in growth plates

• the collagenous matrix in growth plates lacks structural continuity and the longitudinal septa are irregularly thickened

• polarity of proliferating chondrocytes and periarticular chondrocytes in the growth plates is not clearly defined

• the parallel organization of primary cilia in chondrocytes of the growth plates of newborns is not clearly established and the uniform pattern of primary cilia alignment in growth plates of 10 week old mice is not apparent

abnormal long bone hypertrophic chondrocyte zone ( J:216945 )

• 10 week old mice show irregular distribution of collagen X-rich matrix in the hypertrophic zones

disorganized long bone epiphyseal plate ( J:216945 )

• tibial growth plates show disorganized columnar chondrocytes whose continuity of the typical palisade-like arrangement is often interrupted by extended areas in which chondrocytes are absent

decreased length of long bones ( J:216945 )

short femur ( J:216945 )

short tibia ( J:216945 )

abnormal vertebrae morphology ( J:216945 )

• vertebrae are shorter and wider

abnormal bone collagen fibril morphology ( J:216945 )

• diameter of collagen fibrils in the growth plates is small

abnormal chondrocyte morphology ( J:216945 )

• polarity of proliferating chondrocytes and periarticular chondrocytes in the growth plates is not clearly defined

abnormal chondrocyte physiology ( J:216945 )

• percent of chondrocytes undergoing division is lower in newborn and 10-week old mutants than in controls, indicating decreased proliferation

• an increase in BiP content indicates that chondrocytes are undergoing endoplasmic reticulum stress

cellular

abnormal primary cilium morphology ( J:216945 )

• aberrant organization of primary cilia in chondrocytes of growth plates

• length of cilia present in growth plate chondrocytes is reduced

craniofacial

abnormal cranium size ( J:216945 )

• reduction in length/width ratio of the skull

limbs/digits/tail

short femur ( J:216945 )

increased diameter of femur ( J:216945 )

increased diameter of tibia ( J:216945 )

short tibia ( J:216945 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spondyloepiphyseal dysplasia congenita		DOID:14789	OMIM:183900	J:216945

Genotype
MGI:4429125

cn14

• Allelic Composition: Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Tg(Col2a1-cre)1Bhr/0; Tg(tetO-Vegfa)90Ala/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N * SJL

skeleton

abnormal long bone metaphysis morphology ( J:156474 )

• doxycycline-treated mice exhibit a increase metaphyseal microvascular density compared to in wild-type mice

abnormal bone structure ( J:156474 )

• following doxycycline treatment for the first 2 weeks of life, growing long bones are abnormal in shape and morphology with abundant stromal cells and blood vessels surrounding numerous trabeculae unlike in wild-type mice

• adult mice treated with doxycycline for 14 days exhibit disrupted bone architecture with abundant peritrabecular mesenchymal stromal cells in the metaphyseal and epiphyseal regions compared with wild-type mice

• adult mice treated with doxycycline for 14 days exhibit lamellar cortical bone is replaced with trabecular-like porous bone structure with abundant intercalating mesenchymal tissue components and osteoclast-rich remodelling units unlike in wild-type mice

decreased osteoclast cell number ( J:156474 )

• doxycycline-treated mice exhibit reduced osteoclast numbers in regions of excessive bone and vascularization compared with wild-type mice

• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment

abnormal bone marrow morphology ( J:156474 )

• in doxycycline-treated mice, bone marrow blood vessels exhibit hemangioma-like morphology and are filled with erythrocytes unlike in wild-type mice

• in doxycycline-treated mice, hematopoietic bone marrow is replaced with new bone, marrow fibrosis, and aberrant blood vessels displaying paucity of myeloid cells unlike in wild-type mice

myelofibrosis ( J:156474 )

• doxycycline-treated mice exhibit bone marrow fibrosis unlike in wild-type mice

abnormal trabecular bone morphology ( J:156474 )

• adult mice treated with doxycycline for 14 days exhibit a 70% increase in trabecular density compared with wild-type mice

increased trabecular bone mass ( J:156474 )

• adult mice treated with doxycycline for 14 days exhibit increased metaphyseal trabecular bone mass compared with wild-type mice

abnormal skeleton development ( J:156474 )

• at E16.5, doxycycline-treated mice exhibit increased cell proliferation in the perichondrium/periosteum and throughout the primary ossification center compared with wild-type mice

• adult mice treated with doxycycline exhibit increased proliferation of the mesenchymal cells in the metaphysis, epiphysis, and periosteum compared with wild-type mice

abnormal osteoblast differentiation ( J:156474 )

• in doxycycline-treated mice as determined by marker expression

abnormal long bone epiphyseal plate morphology ( J:156474 )

• doxycycline-treated mice exhibit a increase in growth plate mineralization compared to in wild-type mice

decreased long bone epiphyseal plate size ( J:156474 )

• doxycycline-treated mice exhibit a mild decrease in growth plate thickness compared to in wild-type mice

abnormal bone ossification ( J:156474 )

• increased following doxycycline treatment

decreased bone resorption ( J:156474 )

• doxycycline-treated mice exhibit reduced bone resorption in the diaphyses and metaphysis compared with wild-type mice

• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment

hematopoietic system

abnormal hematopoietic system morphology/development ( J:156474 )

• doxycycline-treated mice exhibit an increase in CFU-Cs (colony-forming units in culture) in the peripheral blood and spleen compared with wild-type mice

• however, bone marrow CFUs of doxycycline-treated mice are normal

enlarged spleen ( J:156474 )

• in 25% of doxycycline-treated mice indicating extramedullary hematopoiesis

extramedullary hematopoiesis ( J:156474 )

• as indicated by enlarged spleen size in 25% of doxycycline-treated mice

increased megakaryocyte cell number ( J:156474 )

• in the spleen of doxycycline-treated mice

abnormal megakaryocyte progenitor cell morphology ( J:156474 )

• the number of megakarypcyte and progenitor cells in the spleens of doxycycline-treated mice is increased compared to in wild-type mice

thrombocytopenia ( J:156474 )

• small after 2 weeks of doxycycline treatment

decreased osteoclast cell number ( J:156474 )

• doxycycline-treated mice exhibit reduced osteoclast numbers in regions of excessive bone and vascularization compared with wild-type mice

• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment

increased hematopoietic stem cell number ( J:156474 )

• in the peripheral blood of doxycycline-treated mice

cardiovascular system

abnormal vasculogenesis ( J:156474 )

• following doxycycline treatment, bone vasculogenesis is increased compared to in wild-type mice

• in doxycycline treated mice, bone marrow blood vessels exhibit hemangioma-like morphology and are filled with erythrocytes unlike in wild-type mice

immune system

enlarged spleen ( J:156474 )

• in 25% of doxycycline-treated mice indicating extramedullary hematopoiesis

decreased osteoclast cell number ( J:156474 )

• doxycycline-treated mice exhibit reduced osteoclast numbers in regions of excessive bone and vascularization compared with wild-type mice

• however, osteoclast coverage and bone remodeling are normal in the cortical regions of bone following doxycycline treatment

cellular

abnormal osteoblast differentiation ( J:156474 )

• in doxycycline-treated mice as determined by marker expression

growth/size/body

enlarged spleen ( J:156474 )

• in 25% of doxycycline-treated mice indicating extramedullary hematopoiesis

Genotype
MGI:4429123

cn15

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Vegfa*)Jhai}/Gt(ROSA)26Sor⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * ICR * SJL

mortality/aging

perinatal lethality, complete penetrance ( J:156474 )

• mice die at birth

skeleton

abnormal long bone morphology ( J:156474 )

• long bones are abnormal and bent (kyphosis) compared to in wild-type mice

• however, skeletal patterning and growth is normal

abnormal long bone diaphysis morphology ( J:156474 )

• at E16.5, limb diaphyses are short and thick compared to in wild-type mice

• at E16.5, primary ossification centers are malformed compared to in wild-type mice

• at E16.5, ossification centers are laterally expanded with excessive, disorganized bone compared to in wild-type mice

decreased width of hypertrophic chondrocyte zone ( J:156474 )

• mild

abnormal rib morphology ( J:156474 )

• at E16.5, rib diaphyses are short and thick compared to in wild-type mice

abnormal bone structure ( J:156474 )

• at E16.5, limb and rib diaphyses are short and thick compared to in wild-type mice

• bone lack a proper cortex and abnormally oriented trabecular-like structures extend inside the bone, obliterating the developing marrow cavity unlike in wild-type mice

• mice exhibit increased blood vessels in the bone compared with wild-type mice

abnormal bone marrow cavity morphology ( J:156474 )

• abnormally oriented trabecular-like structures extend inside the bone, obliterating the developing marrow cavity unlike in wild-type mice

abnormal bone ossification ( J:156474 )

• at E16.5, primary ossification centers are malformed compared to in wild-type mice

• at E16.5, ossification centers are laterally expanded with excessive, disorganized bone compared to in wild-type mice

Genotype
MGI:4429126

cn16

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Vegfa*)Jhai}/Gt(ROSA)26Sor⁺; Kdr^tm1Wag/Kdr^tm1Wag; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * ICR * SJL

skeleton

skeleton phenotype ( J:156474 )

N • mice do not exhibit severe long bone kyphosis unlike in Gt(ROSA)26Sor^tm1Jhai Tg(Col2a1-cre)1Bhr mice

abnormal long bone diaphysis morphology ( J:156474 )

• bone shafts in mice are wider than in wild-type mice

abnormal bone structure ( J:156474 )

• mice exhibit hypervascularization in the expanded perichondrial/periosteal region and inside the bone shaft compared with wild-type mice

increased bone mass ( J:156474 )

• mice exhibit an increase in mineralized bone formed compared with wild-type mice that is not as severe as in Gt(ROSA)26Sor^tm1Jhai Tg(Col2a1-cre)1Bhr mice

abnormal skeleton development ( J:156474 )

• mesenchymal hyperproliferation in mice is reduced compared to in Gt(ROSA)26Sor^tm1Jhai Tg(Col2a1-cre)1Bhr mice

cardiovascular system

abnormal blood vessel morphology ( J:156474 )

• mice exhibit hypervascularization in the expanded perichondrial/periosteal region and inside the bone shaft compared with wild-type mice

Genotype
MGI:3813812

cn17

• Allelic Composition: Vdr^tm1Gcm/Vdr^tm1Gcm; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

skeleton

decreased osteoclast cell number ( J:117377 )

• osteoclast numbers in the primary ossification centers of E15.5 tibiae are reduced by two-thirds

• the number of osteoblasts found at the border of the tibiae growth plate is decreased by 50%

• the osteoclast surface area in trabecular bone in 15 day old mice is decreased by a third

abnormal trabecular bone morphology ( J:117377 )

• there is a 50% increase in trabecular bone volume in neonates and in 15 day old mice

• the trabecular bone extends more deeply into the metaphyseal area of the proximal tibiae in 15 day old mice

• the growth plate of cancellous bone has less blood vessel invasion and fewer osteoblasts associated with it

delayed endochondral bone ossification ( J:117377 )

• trabecular ossification is delayed with smaller ossification centers occurring in the tibiae of E15.5 mice

homeostasis/metabolism

abnormal vitamin D level ( J:117377 )

• mean serum levels of the active form of vitamin D are 127.4 pg/ml compared to 74.88 pg/ml in wild-type mice at 15 days of age

• levels normalize by adulthood

abnormal mineral homeostasis ( J:117377 )

• levels of circulating FGF23, which regulates phosphate homeostasis, is decreased by 43% in 15 day old mice compared to wild-type controls

• levels normalize by adulthood

increased circulating phosphate level ( J:117377 )

• phosphate levels are 14.33 mg/ml compared to 12.87 mg/ml in wild-type controls at 15 days of age

• levels normalize by adulthood

hematopoietic system

decreased osteoclast cell number ( J:117377 )

• osteoclast numbers in the primary ossification centers of E15.5 tibiae are reduced by two-thirds

• the number of osteoblasts found at the border of the tibiae growth plate is decreased by 50%

• the osteoclast surface area in trabecular bone in 15 day old mice is decreased by a third

cardiovascular system

decreased angiogenesis ( J:117377 )

• invasion of blood vessels from the perichondrium into the cartilage core is reduced by a third in tibiae growth plate of E15.5 mice

• in neonatal tibiae, the number of blood vessels invading the terminal row of the hypertrophic chondrocytes of the growth plate is reduced

• the intercapillary distance is significantly increased both at the terminal row of the growth plate and in the metaphysis of 15 day old mice

immune system

decreased osteoclast cell number ( J:117377 )

• osteoclast numbers in the primary ossification centers of E15.5 tibiae are reduced by two-thirds

• the number of osteoblasts found at the border of the tibiae growth plate is decreased by 50%

• the osteoclast surface area in trabecular bone in 15 day old mice is decreased by a third

Genotype
MGI:4437602

cn18

• Allelic Composition: Ext1^tm1Vcs/Ext1⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

preweaning lethality, complete penetrance ( J:157599 )

• no animals are recovered at weaning

Genotype
MGI:3710959

cn19

• Allelic Composition: Kif3a^tm2Gsn/Kif3a^tm2Gsn; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

skeleton

spina bifida occulta ( J:121342 )

• at P30, failure of fusion in the dorsal vertebrae

abnormal long bone epiphyseal plate morphology ( J:121342 )

• at P10, the growth plate has altered columnar organization and is discontinuous across the width of the skeletal elements with continuous primary and secondary ossification centers in areas where the growth plate is missing

• at P15, growth plate structure is completely abrogated with ossification centers merged and the distance from the articular surface to the trabecular bone is reduced

• at P30, growth plates in the long bones are missing

abnormal long bone epiphyseal plate proliferative zone ( J:121342 )

• at P7, the length of the zone of flat proliferating cells is reduced

• at P7 and P10 fewer cells are undergoing mitosis (pH3+) in the growth plate (86% and 78%, respectively)

• at P10, columnar alignment of the proliferating cells is lost with abnormal movement of the cells during rotation despite intact polarity of the cells

• at P15, no mitosis is detected, cells have a round morphology and lack polarity

abnormal long bone hypertrophic chondrocyte zone ( J:121342 )

• at P15, hypertrophic cells invade the prehypertrophic zones

abnormal long bone epiphysis morphology ( J:121342 )

• at P7, reduction of the epiphysis is due to reduction in the flat chondrocyte regions without a reduction in the length of the hypertrophic zone

• at P10, the length is reduced; however, the width is increased

• at P30, the growth plates in the long bones are missing

• however, the length of long bones and the levels of ossification are no different than in wild-type mice at E18.5 and P0

decreased length of long bones ( J:121342 )

abnormal rib morphology ( J:121342 )

• at P30, ribs are small and deformed

thoracic vertebral fusion ( J:121342 )

• sporadic at P30

abnormal chondrocyte morphology ( J:121342 )

• at E15.5, P0 and P7, 80% reduction in the number of chondrocytes with cilia

• however, perichondrial cells have cilia

• at P10, the actin cytoskeleton in chondrocytes is disorganized

nervous system

spina bifida occulta ( J:121342 )

• at P30, failure of fusion in the dorsal vertebrae

growth/size/body

disproportionate dwarf ( J:121342 )

• at P30, dwarfism occurs in which there is a 32% reduction in crown to rump and limb length

embryo

spina bifida occulta ( J:121342 )

• at P30, failure of fusion in the dorsal vertebrae

cellular

abnormal actin cytoskeleton morphology ( J:121342 )

• at P10, the actin cytoskeleton in chondrocytes is disorganized

Genotype
MGI:7279112

cn20

• Allelic Composition: Mapk8^tm1Rjd/Mapk8^tm1Rjd; Mapk9^tm1Flv/Mapk9^tm1Flv; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL

mortality/aging

premature death ( J:277201 )

• need to be euthanized at approximately 10 weeks of age due to urinary retention and paraphimosis

renal/urinary system

paraphimosis ( J:277201 )

ischuria ( J:277201 )

• urinary retention

skeleton

abnormal knee joint morphology ( J:277201 )

• the articular cartilage thickness, the width of the joint at the level of the femoral condyles, and the height of the tibial plateau are decreased

abnormal sternebra morphology ( J:277201 )

• enlargement of the growth plate

sternebra fusion ( J:277201 )

• at 10 weeks of age

abnormal sternocostal joint morphology ( J:277201 )

• separation at the joints is not well defined at 10 weeks of age

abnormal intervertebral disk morphology ( J:277201 )

• ectopic ossification localized in the caudal thoracic and thoracic spine at 4 weeks of age

• the typical lamellar structure of the annulus fibrosus is completely absent at 4 weeks of age

• at 10 weeks of age in the proximal thoracic spine (approximately cranial to T9) disks are replaced by a proteoglycan-rich cartilaginous tissue that extends beyond the disk and appears to connect the distal and proximal growth plates of adjacent vertebral bodies

• at E15.5 and E17.5, the annulus fibrosus is populated by larger, chondrocyte-like cells with altered alignment of the collagen fibers in the laminae

• increased annulus fibrosus width for both dorsal and ventral regions at E17.5

abnormal nucleus pulposus morphology ( J:277201 )

• reduced in size at 4 weeks of age

calcified intervertebral disk ( J:277201 )

• seen at P11

• at 10 weeks of age most of the area of the disks is completely replaced with bone and cartilage in the lumbar and caudal thoracic spine

scoliosis ( J:277201 )

• seen at 4 weeks of age with Cobb angles ranging from 40 to 92 degrees

abnormal vertebrae morphology ( J:277201 )

• ectopic ossification in multiple structures of the vertebrae including the transverse and spinous processes

abnormal vertebral epiphyseal plate morphology ( J:277201 )

• decreased length at E17.5

vertebral fusion ( J:277201 )

• fused vertebrae with no space where the intervertebral disks should be

• fusions in the transverse and spinous processes are seen at P11 with the most advanced lesions seen in the lumbar spine

fusion of vertebral arches ( J:277201 )

• seen at E17.5 along with abnormally shaped primary ossification centers

fusion of vertebral bodies ( J:277201 )

• fusions of bodies and posterior elements are detected in the lumbar and thoracic spine

growth/size/body

decreased body size ( J:277201 )

distended abdomen ( J:277201 )

• at weaning

behavior/neurological

abnormal gait ( J:277201 )

• at weaning

limbs/digits/tail

abnormal knee joint morphology ( J:277201 )

• the articular cartilage thickness, the width of the joint at the level of the femoral condyles, and the height of the tibial plateau are decreased

abnormal tail position or orientation ( J:277201 )

• upward tail orientation

reproductive system

paraphimosis ( J:277201 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
scoliosis		DOID:0060249		J:277201

Genotype
MGI:5426513

cn21

• Allelic Composition: Fgfr3^tm2Llm/Fgfr3⁺; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

growth/size/body

decreased body size ( J:183772 )

• dwarfism

skeleton

abnormal long bone morphology ( J:183772 )

decreased length of long bones ( J:183772 )

abnormal axial skeleton morphology ( J:183772 )

abnormal craniofacial bone morphology ( J:183772 )

domed cranium ( J:183772 )

abnormal thoracic cage morphology ( J:183772 )

• narrow trunk

short ribs ( J:183772 )

abnormal bone structure ( J:183772 )

increased osteoclast cell number ( J:183772 )

• osteoclasts per bone area are increased

• osteoclast surface area/bone surface area is increased

abnormal trabecular bone morphology ( J:183772 )

• fewer subchondral trabeculae

• trabeculae only partially mineralized

• more abundant collagen deposition

• significantly lower bone volume/trabecular volume in distal metaphysis of the femur

abnormal skeleton development ( J:183772 )

abnormal long bone epiphyseal plate morphology ( J:183772 )

abnormal long bone epiphyseal ossification zone morphology ( J:183772 )

• smaller hypertrophic mineralization zone

abnormal long bone epiphyseal plate proliferative zone ( J:183772 )

• lack proliferative column organization

• proliferative zone reduced

decreased width of hypertrophic chondrocyte zone ( J:183772 )

• reduced hypertrophic zone

• small hypertrophic cells

abnormal long bone epiphysis morphology ( J:183772 )

• reduced size of epiphysis

abnormal bone mineralization ( J:183772 )

• defect in mineralization of calcified cartilage and primary spongiosa

delayed bone ossification ( J:183772 )

• delayed formation of secondary ossification centers

craniofacial

abnormal craniofacial bone morphology ( J:183772 )

domed cranium ( J:183772 )

hematopoietic system

increased osteoclast cell number ( J:183772 )

• osteoclasts per bone area are increased

• osteoclast surface area/bone surface area is increased

immune system

increased osteoclast cell number ( J:183772 )

• osteoclasts per bone area are increased

• osteoclast surface area/bone surface area is increased

Genotype
MGI:5293349

cn22

• Allelic Composition: Sox9^tm4.1Tlu/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL

skeleton

skeleton phenotype ( J:176950 )

N • forelimbs are unaffected

abnormal vertebrae development ( J:176950 )

• intermediate premature ossification at E17.5 in the vertebra

• however, the lumbar vertebra exhibit normal ossification

premature endochondral bone ossification ( J:176950 )

• intermediate at E17.5 in the vertebra

• however, the lumbar vertebra exhibit normal ossification

behavior/neurological

hunched posture ( J:176950 )

growth/size/body

decreased body size ( J:176950 )

Genotype
MGI:5293350

cn23

• Allelic Composition: Sox9^tm4.1Tlu/Sox9^tm4.1Tlu; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL

skeleton

short humerus ( J:176950 )

short radius ( J:176950 )

short ulna ( J:176950 )

scapular bone hypoplasia ( J:176950 )

abnormal vertebrae development ( J:176950 )

• severe premature ossification at E17.5 in the vertebra

abnormal vertebral body morphology ( J:176950 )

premature endochondral bone ossification ( J:176950 )

• severe at E17.5 in the vertebra

limbs/digits/tail

abnormal forelimb stylopod morphology ( J:176950 )

• foreshortened long bones

short humerus ( J:176950 )

abnormal forelimb zeugopod morphology ( J:176950 )

• foreshortened long bones

short radius ( J:176950 )

short ulna ( J:176950 )

Genotype
MGI:5306893

cn24

• Allelic Composition: Casr^tm1Wch/Casr^tm1Wch; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:180651 )

• no mice are detected between E14 and E16

embryonic lethality during organogenesis, incomplete penetrance ( J:180651 )

• only 2 mice are detected between E12 and E13

skeleton

abnormal skeleton development ( J:180651 )

• at E12.5, the two surviving mice exhibit short skeletons compared with control mice

decreased bone mineralization ( J:180651 )

• mice exhibit poorly mineralized rib cages, calvariae, and long bones compared with control mice

Genotype
MGI:5086010

cn25

• Allelic Composition: Amer1^tm1.1Nbar/Y; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

skeleton

skeleton phenotype ( J:173242 )

♂N • no gross skeletal defects are detected

Genotype
MGI:6284806

cn26

• Allelic Composition: Dot1l^{tm1c(KOMP)Wtsi}/Dot1l^{tm1c(KOMP)Wtsi}; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * C57BL/6N * SJL

growth/size/body

postnatal growth retardation ( J:246059 )

• at 4 weeks of age, mice exhibit severe growth retardation, as shown by skeletal staining and histology of the growth plate

• however, no skeletal abnormalities are observed

skeleton

abnormal long bone epiphyseal plate morphology ( J:246059 )

• TCF1 levels are increased in the growth plate, indicating Wnt pathway activation

• COLX (type X collagen) levels are increased in the growth plate with no apparent changes in MMP-13 (matrix metallopeptidase 13) levels

abnormal long bone epiphyseal plate proliferative zone ( J:246059 )

• histology of the growth plates revealed a reduced and disorganized proliferative and prehypertrophic zone at 4 weeks of age

abnormal articular cartilage morphology ( J:246059 )

• TCF1 levels are increased in articular cartilage, indicating Wnt pathway activation

• COLX and MMP-13 levels appear to be increased in articular cartilage, indicating accelerated chondrocyte hypertrophy

Genotype
MGI:3056288

cn27

• Allelic Composition: Ctnnb1^tm1Yy/Ctnnb1^tm1Yy; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:93028 )

• mutants die shortly after birth

craniofacial

domed cranium ( J:93028 )

limbs/digits/tail

short limbs ( J:93028 )

skeleton

domed cranium ( J:93028 )

fused synovial joints ( J:93028 )

• the calcaneus is fused to the cuboid and the navicular is partially fused to the intermediate cuneiforms at E15.5

Genotype
MGI:5505276

cn28

• Allelic Composition: Serpinh1^tm2Kzn/Serpinh1^tm2Kzn; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL

mortality/aging

perinatal lethality, complete penetrance ( J:197791 )

• at E18.5 due to severe amnionic bleeding and remaining mice die just before or within 2 hours of birth

skeleton

skeleton phenotype ( J:197791 )

N • mice exhibit normal sized cranial bone

hemarthrosis ( J:197791 )

• bleeding in the shoulder, elbow and knee joints of some mice at E18.5 and P0

abnormal elbow joint morphology ( J:197791 )

• elbow joints lack cavities found in control mice joints; also observed in other joints

abnormal long bone morphology ( J:197791 )

• abnormal at E15.0 and E18.5

• shorter and twisted

abnormal phalanx morphology ( J:197791 )

• uncalcified foreleg phalanges

abnormal humerus morphology ( J:197791 )

• disorganized

short humerus ( J:197791 )

• shorter and twisted compared to in control mice

short radius ( J:197791 )

• shorter and twisted compared to in control mice

short ulna ( J:197791 )

• shorter and twisted compared to in control mice

short femur ( J:197791 )

• shorter and twisted compared to in control mice

short fibula ( J:197791 )

• shorter and twisted compared to in control mice

short tibia ( J:197791 )

• shorter and twisted compared to in control mice

abnormal thoracic cage morphology ( J:197791 )

abnormal spine curvature ( J:197791 )

• severely twisted cervical, lumbar and sacral spine at E14.5 to E18.5 and in neonates

kyphosis ( J:197791 )

abnormal vertebral arch morphology ( J:197791 )

• failure of sacral vertebral arches to fuse

abnormal chondrocyte morphology ( J:197791 )

• chondrocytes exhibit decreased collagen secretion and distended rough endoplasmic reticulum with defects in collagen fibrillar formation compared with control cells

abnormal skeleton development ( J:197791 )

• fewer bones are visible by CT scanning compared with wild-type mice

abnormal rib development ( J:197791 )

• rib cartilage is shorter and twisted compared to in control mice

chondrodystrophy ( J:197791 )

• severe and systemic at E15.0 and E18.5 with reduced collagen accumulation

abnormal bone ossification ( J:197791 )

• impaired ossification of the vertebral bodies of the thoracic, lumbar, sacral and caudal vertebrae

• ectopic ossification of cervical vertebrae

delayed bone ossification ( J:197791 )

• impaired ossification of the vertebral bodies of the thoracic, lumbar, sacral and caudal vertebrae

delayed endochondral bone ossification ( J:197791 )

limbs/digits/tail

abnormal limb morphology ( J:197791 )

• severely twisted and deformed limbs, some of which bleed in the joint region

abnormal phalanx morphology ( J:197791 )

• uncalcified foreleg phalanges

abnormal elbow joint morphology ( J:197791 )

• elbow joints lack cavities found in control mice joints; also observed in other joints

abnormal humerus morphology ( J:197791 )

• disorganized

short humerus ( J:197791 )

• shorter and twisted compared to in control mice

short radius ( J:197791 )

• shorter and twisted compared to in control mice

short ulna ( J:197791 )

• shorter and twisted compared to in control mice

short femur ( J:197791 )

• shorter and twisted compared to in control mice

short fibula ( J:197791 )

• shorter and twisted compared to in control mice

short tibia ( J:197791 )

• shorter and twisted compared to in control mice

respiratory system

abnormal respiratory system morphology ( J:197791 )

• narrow airway

abnormal bronchial cartilage morphology ( J:197791 )

respiratory distress ( J:197791 )

craniofacial

cleft palate ( J:197791 )

short snout ( J:197791 )

growth/size/body

cleft palate ( J:197791 )

short snout ( J:197791 )

decreased birth weight ( J:197791 )

cardiovascular system

hemorrhage ( J:197791 )

• severe amnionic bleeding at E18.5 in some mice

hemarthrosis ( J:197791 )

• bleeding in the shoulder, elbow and knee joints of some mice at E18.5 and P0

embryo

persistence of notochord tissue ( J:197791 )

• the notochords remains as rod-like axial structures at E14.5

digestive/alimentary system

cleft palate ( J:197791 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta type 10		DOID:0110346	OMIM:613848	J:197791

Genotype
MGI:3640323

cn29

• Allelic Composition: Fgfr3^tm4Cxd/Fgfr3⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * NIH Black Swiss * SJL

mortality/aging

neonatal lethality, incomplete penetrance ( J:63198 )

• majority die on the first day after birth

skeleton

abnormal skeleton morphology ( J:63198 )

• exhibit skeletal phenotypes similar to heterozygous Fgfr3^tm4.1Cxd mice

respiratory system

impaired lung alveolus development ( J:63198 )

• P1 lungs show reduced alveoli formation similar to that seen in heterozygous Fgfr3^tm4.1Cxd mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thanatophoric dysplasia		DOID:13481	OMIM:187600 OMIM:187601 OMIM:273680	J:63198

Genotype
MGI:3687747

cn30

• Allelic Composition: Ctnnb1^tm1Yy/Ctnnb1^tm1.1Yy; Ptch1^tm1Yy/Ptch1^tm1.1Yy; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

cellular

arrested osteoblast differentiation ( J:112462 )

• osteoblast differentiation is severely blocked and mature osteoblasts are almost completely absent in E16.5 embryo limbs

skeleton

arrested osteoblast differentiation ( J:112462 )

• osteoblast differentiation is severely blocked and mature osteoblasts are almost completely absent in E16.5 embryo limbs

abnormal elbow joint morphology ( J:112462 )

• the elbow joint interzone fails to form

abnormal long bone hypertrophic chondrocyte zone ( J:112462 )

• chondrocyte hypertrophy is inhibited

fused synovial joints ( J:112462 )

• show extensive synovial joint fusions which are much more severe than in each of the single mutants

abnormal perichondrium morphology ( J:112462 )

• perichondrium is thinner

decreased bone mineralization ( J:112462 )

• mineralization in the long bones is more severely reduced than in single conditional Ctnnb1 mutants

delayed endochondral bone ossification ( J:112462 )

• ossification is more severely inhibited than in single conditional Ctnnb1 mutants

craniofacial

craniofacial phenotype ( J:112462 )

N • exhibit normal posterior skull formation

limbs/digits/tail

abnormal elbow joint morphology ( J:112462 )

• the elbow joint interzone fails to form

Genotype
MGI:3687748

cn31

• Allelic Composition: Ctnnb1^tm1Yy/Ctnnb1^tm1.1Yy; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

cellular

increased chondrocyte apoptosis ( J:112462 )

• exhibit extensive cell death in both proliferative and resting chondrocytes at E18.5

skeleton

increased chondrocyte apoptosis ( J:112462 )

• exhibit extensive cell death in both proliferative and resting chondrocytes at E18.5

abnormal perichondrium morphology ( J:112462 )

• perichondrium is thinner

decreased bone mineralization ( J:112462 )

• mineralization is decreased

failure of bone ossification ( J:112462 )

• ossification is inhibited

Genotype
MGI:3846228

cn32

• Allelic Composition: Mbtps1^tm1Jdh/Mbtps1^tm1Jdh; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

Severe chondrodysplasia in Mbtps1^tm1Jdh/Mbtps1^tm1Jdh Tg(Col2a1-cre)1Bhr/0 mice

mortality/aging

neonatal lethality, complete penetrance ( J:135374 )

• mice die during or shortly after birth

skeleton

abnormal skeleton morphology ( J:135374 )

• all skeletal elements are smaller than in wild-type mice

short basicranium ( J:135374 )

• the chondro-cranial base is shortened compared to in wild-type mice

small cranium ( J:135374 )

short mandible ( J:135374 )

short maxilla ( J:135374 )

abnormal skeleton development ( J:135374 )

• at E14.5, endochondral chondrocytes fail to exhibit a change from proliferation to hypertrophic cells unlike in wild-type mice

abnormal long bone hypertrophic chondrocyte zone ( J:135374 )

• at E15.5, mice lack an organized hypertrophic zone unlike wild-type mice

• differentiation of hypertrophic chonndrocytes is incomplete

• chondrocytes exhibit abnormal mineralization that precludes vascularization of skeletal elements

chondrodystrophy ( J:135374 )

abnormal skeleton physiology ( J:135374 )

• the skull bones exhibit increased sensitivity to potassium hydroxide compared to wild-type bones

abnormal bone mineralization ( J:135374 )

• mice exhibit abnomal mineralization of hypertrophic chondrocytes in long bones that is associated with increased chondrocyte apoptosis unlike in wild-type mice

failure of endochondral bone ossification ( J:135374 )

growth/size/body

protruding tongue ( J:135374 )

• mice are born with protruding tongues

decreased birth body size ( J:135374 )

• mice are small at birth

abnormal chest morphology ( J:135374 )

• the chest cavity is small and compresses the internal organs into the abdominal cavity unlike in wild-type mice

distended abdomen ( J:135374 )

craniofacial

short basicranium ( J:135374 )

• the chondro-cranial base is shortened compared to in wild-type mice

small cranium ( J:135374 )

short mandible ( J:135374 )

short maxilla ( J:135374 )

protruding tongue ( J:135374 )

• mice are born with protruding tongues

digestive/alimentary system

protruding tongue ( J:135374 )

• mice are born with protruding tongues

limbs/digits/tail

abnormal limb morphology ( J:135374 )

• the orientation of the limbs is skewed likely due to abnormal articular joint development

Genotype
MGI:3785772

cn33

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

Skeletal abnormalities in Bmpr1b^tm1Kml/Bmpr1b^tm1Kml, Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col2a1-cre)1Bhr/?, and Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Col2a1-cre)1Bhr/? mice

mortality/aging

postnatal lethality ( J:97410 )

skeleton

decreased length of long bones ( J:97410 )

abnormal thoracic cage shape ( J:97410 )

• rib cage is flattened

small thoracic cage ( J:97410 )

• rib cage is smaller and flattened

chondrodystrophy ( J:97410 )

• generalized chondrodysplasia

delayed bone ossification ( J:97410 )

respiratory system

respiratory distress ( J:97410 )

• respiratory distress due to smaller and flattened rib cage

Genotype
MGI:2451169

cn34

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:79879 )

• 95% of animals die 10 days after birth; only a few survive and are able to mate

growth/size/body

disproportionate dwarf ( J:79879 )

skeleton

kyphosis ( J:79879 )

abnormal vertebrae morphology ( J:79879 )

• compression of cervical and thoracic verterbrae

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:79879

Genotype
MGI:3769501

cn35

• Allelic Composition: Gt(ROSA)26Sor^tm1(Wnt4)Bhr/Gt(ROSA)26Sor⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

Growth defects in Gt(ROSA)26Sor^tm1(Wnt4)Bhr/Gt(ROSA)26Sor⁺ Tg(Col2a1-cre)1Bhr/0 mice

cellular

decreased chondrocyte proliferation ( J:129327 )

• chondrocytes are proliferating 36% slower than controls at two weeks of age

growth/size/body

long incisors ( J:129327 )

• protruding incisors are observed in nine month old mice

short nasal bone ( J:129327 )

• nasal bones of six week old mice are significantly shortened

decreased body weight ( J:129327 )

• male mice are 50-60% of the bodyweight as age-matched controls

• female mice are 60-70% of the bodyweight as age-matched controls

disproportionate dwarf ( J:129327 )

• mice are undersized with shortened axial skeletons, altered head shape and disproportionately shorter limbs

skeleton

decreased chondrocyte proliferation ( J:129327 )

• chondrocytes are proliferating 36% slower than controls at two weeks of age

abnormal craniofacial bone morphology ( J:129327 )

small frontal bone ( J:129327 )

• frontal bones are slightly smaller

small occipital bone ( J:129327 )

• occipital are slightly smaller

long incisors ( J:129327 )

• protruding incisors are observed in nine month old mice

short nasal bone ( J:129327 )

• nasal bones of six week old mice are significantly shortened

domed cranium ( J:129327 )

• the skulls have a dome-shaped neurocranium vault

abnormal pubis morphology ( J:129327 )

• the pubic and ischial bones have failed to fuse at six weeks of age

• ossification of the bones occurs by 8 weeks of age but the pubic bone is still thinner

kyphosis ( J:129327 )

• is observed in nine-month old mice

short lumbar vertebrae ( J:129327 )

• vertebrae are narrow and flat caused by a reduction in lateral bone

axial skeleton hypoplasia ( J:129327 )

• axial skeletion is shortened compared to wild-type controls

abnormal bone marrow morphology ( J:129327 )

• the tibiae are deficient in bone marrow and are instead filled with adipocytes at 9 months of age

abnormal cartilage morphology ( J:129327 )

increased width of hypertrophic chondrocyte zone ( J:129327 )

• found in mice two weeks of age

disorganized long bone epiphyseal plate ( J:129327 )

• found in mice two weeks of age with less columnar organization

abnormal chondrocyte morphology ( J:129327 )

• less vascular endothelium growth factor is expressed by cells in the chondrocyte zones of the tibiae

delayed endochondral bone ossification ( J:129327 )

• primary ossification centers do not form in the tibiae until after E15.5

• formation of secondary ossification centers in the tibiae are delayed by four days

craniofacial

abnormal craniofacial bone morphology ( J:129327 )

small frontal bone ( J:129327 )

• frontal bones are slightly smaller

small occipital bone ( J:129327 )

• occipital are slightly smaller

long incisors ( J:129327 )

• protruding incisors are observed in nine month old mice

short nasal bone ( J:129327 )

• nasal bones of six week old mice are significantly shortened

domed cranium ( J:129327 )

• the skulls have a dome-shaped neurocranium vault

limbs/digits/tail

short limbs ( J:129327 )

• visibly shorter

behavior/neurological

decreased locomotor activity ( J:129327 )

• slow movement, which is possibly a result of the abnormal skeletal features

respiratory system

short nasal bone ( J:129327 )

• nasal bones of six week old mice are significantly shortened

Genotype
MGI:2451170

cn36

• Allelic Composition: Sox9^tm2Crm/Sox9^tm2Crm; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:79879 )

• embryos die around day E16.5; only a few are recovered after birth

craniofacial

short snout ( J:79879 )

growth/size/body

short snout ( J:79879 )

decreased body length ( J:79879 )

distended abdomen ( J:79879 )

limbs/digits/tail

short limbs ( J:79879 )

short tail ( J:79879 )

skeleton

chondrodystrophy ( J:79879 )

• severe

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:79879

Genotype
MGI:3785771

cn37

• Allelic Composition: Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr; Bmpr1b^tm1Kml/Bmpr1b^tm1Kml; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * SJL

Skeletal abnormalities in Bmpr1b^tm1Kml/Bmpr1b^tm1Kml, Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Tg(Col2a1-cre)1Bhr/?, and Bmpr1a^tm2.1Bhr/Bmpr1a^tm2.1Bhr Bmpr1b^tm1Kml/Bmpr1b^tm1Kml Tg(Col2a1-cre)1Bhr/? mice

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:97410 )

• lethality between E17.5 and birth, due to compression of internal organs and eventual heart failure

growth/size/body

short snout ( J:97410 )

• embryos develop short snouts

decreased fetal size ( J:97410 )

• mutants are reduced in size starting at E13.5

embryo

abnormal notochord morphology ( J:97410 )

• notochord at E14.5 is disorganized and is embedded within a layer of dense fibroblasts

skeleton

decreased radius size ( J:97410 )

• small radius

abnormal ulna morphology ( J:97410 )

• small ulna

abnormal vertebral column morphology ( J:97410 )

• vertebral column is completely absent at E14.5

abnormal chondrocyte morphology ( J:97410 )

• chondrocytes undergo random and disorganized hypertrophy at P0

abnormal skeleton development ( J:97410 )

abnormal vertebrae development ( J:97410 )

• no vertebrae form by E13.5

abnormal cartilage development ( J:97410 )

• cartilage elements exhibit reduced rates of proliferation from E13.5 to E16.5 and increased cell apoptosis

• cartilage elements are severely disorganized and do not produce cartilage specific extracellular matrix

abnormal chondrocyte differentiation ( J:97410 )

• chondrocyte differentiation is impaired, with appendicular and nasal cavity condensations remaining in a prechondrocytic state

• although cells in prechondrocytic condensations eventually differentiate, they do not undergo the organized differentiation program found in the growth plate

abnormal epiphyseal plate morphology ( J:97410 )

• the few cartilage condensations that do form are delayed in the prechondrocytic state and never form an organized growth plate

chondrodystrophy ( J:97410 )

• severe generalized chondrodysplasia

failure of endochondral bone ossification ( J:97410 )

• majority of skeletal elements that form through endochondral ossification are absent and the ones that form are rudimentary and malformed

limbs/digits/tail

decreased radius size ( J:97410 )

• small radius

abnormal ulna morphology ( J:97410 )

• small ulna

abnormal digit development ( J:97410 )

• digits by E14.5 have fully formed pericondria but cells within the cores do not exhibit prechondrocyte characteristics

short limbs ( J:97410 )

• embryos develop short limbs

short tail ( J:97410 )

• embryos develop short tails

craniofacial

short snout ( J:97410 )

• embryos develop short snouts

Genotype
MGI:3719016

cn38

• Allelic Composition: Mef2c^tm1Eno/Mef2c^tm2Eno; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * SJL

skeleton

decreased length of long bones ( J:119152 )

• truncation of all long bones of the limbs

abnormal endochondral bone ossification ( J:119152 )

• structures of the distal ribs, radii, and sternabrae are distorted by disorganized cartilaginous remnants of the growth plate and aberrant ossification

failure of sternum ossification ( J:119152 )

• absence of ossification of the sternum and a failure in chondrocyte hypertrophy

behavior/neurological

abnormal gait ( J:119152 )

• waddling gait due to shortened limbs

limbs/digits/tail

short limbs ( J:119152 )

• truncation of all long bones of the limbs

Genotype
MGI:5441473

cn39

• Allelic Composition: Ndrg2^tm1Xzg/Ndrg2^tm1Xzg; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

skeleton

abnormal thoracic vertebrae morphology ( J:187603 )

• T9 is the transitional vertebra in 4 of 15 mice

thoracic vertebral transformation ( J:187603 )

• T13 to L1 transformation in 5 of 15 mice

lumbar vertebral transformation ( J:187603 )

• L6 to S1 transformation in 8 of 15 mice

sacral vertebral transformation ( J:187603 )

• S4 to S3 transformation in 6 of 15 mice

Genotype
MGI:3719017

cn40

• Allelic Composition: Mef2c^tm2Eno/Mef2c^tm2Eno; Mef2d^tm1Eno/Mef2d^tm1Eno; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

skeleton

failure of endochondral bone ossification ( J:119152 )

• nearly all mineralized endochondral skeletons are missing

Genotype
MGI:3641207

cn41

• Allelic Composition: Sox5^tm1Vlf/Sox5^tm1Vlf; Sox6^tm1Vlf/Sox6^tm2.1Vlf; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL

skeleton

abnormal cartilage development ( J:110147 )

• poorly developed cartilage similar to double homozygous mice

Genotype
MGI:6154156

cn42

• Allelic Composition: Trip11^tm1.1Psmi/Trip11^tm1.2Psmi; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/?; Tg(Col2a1-cre)1Bhr/?
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL/J

craniofacial

domed cranium ( J:253969 )

short snout ( J:253969 )

cellular

abnormal Golgi stack morphology ( J:253969 )

• loss of Golgi apparatus stacking found in humeral chondrocytes

respiratory system

impaired lung alveolus development ( J:253969 )

• histology of newborns shows decreased lung alveolar formation relative to controls, which the authors say appears to be secondary to the small ribcage

skeleton

domed cranium ( J:253969 )

decreased length of long bones ( J:253969 )

• newborn pups have shorter bones in the extremities

small thoracic cage ( J:253969 )

abnormal chondrocyte morphology ( J:253969 )

• assessment of chondrocytes in humeri finds swollen chondrocytes in some areas at E15.5 and widespread just after birth, and electron microscopy shows an increase in the size of the endoplasmic reticulum cisternae and disruption of the Golgi stack structure

chondrodystrophy ( J:253969 )

• severe

delayed bone mineralization ( J:253969 )

• newborn pups have decreased mineralization of the skull and vertebral column relative to controls

delayed endochondral bone ossification ( J:253969 )

• E15.5 humeri show delayed formation of the primary ossification center

limbs/digits/tail

short limbs ( J:253969 )

mortality/aging

perinatal lethality, complete penetrance ( J:253969 )

• although generated at the expected Mendelian frequency, these mice all die shortly after birth with severe chondrodysplasia

growth/size/body

short snout ( J:253969 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondrogenesis type IA		DOID:0080054	OMIM:200600	J:253969

Genotype
MGI:3045411

cn43

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129X1/SvJ

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:90567 )

• died around E18.5; only 30% survived after birth

skeleton

decreased length of long bones ( J:90567 )

• endochondral bone elements all shorter

Genotype
MGI:5009239

cn44

• Allelic Composition: Smad1^tm1Abr/Smad1^tm1.1Abr; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: BALB/cJ * C57 * C57BL/6 * SJL

skeleton

abnormal neurocranium morphology ( J:172689 )

• at E16.5, calvarial bone formation and mineralization is reduced compared to in wild-type mice

delayed bone ossification ( J:172689 )

• at E16.5, mice exhibit delayed ossification of the frontal, parietal, and supraoccipital bones compared with wild-type mice

• at E16.5, formation of ossification centers in the proximal phalangeal bones is delayed compared to in wild-type mice

• at E16.5, calvarial bone formation and mineralization is reduced compared to in wild-type mice

• however, embryos appeared normal by E18.5

craniofacial

abnormal neurocranium morphology ( J:172689 )

• at E16.5, calvarial bone formation and mineralization is reduced compared to in wild-type mice

Genotype
MGI:6117390

cn45

• Allelic Composition: Csgalnact1^tm1Nari/Csgalnact1^tm1Nari; Csgalnact2^tm1.1Staka/Csgalnact2^tm1.1Staka; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

mortality/aging

neonatal lethality, incomplete penetrance ( J:256718 )

• 43 of 53 mice die at birth

postnatal lethality, incomplete penetrance ( J:256718 )

• most of the 10 survivors die by P14

respiratory system

respiratory failure ( J:256718 )

• 43 of 53 die from respiratory failure after cesarean section

growth/size/body

decreased body size ( J:256718 )

• severe dwarfism at P7 and P14

decreased body weight ( J:256718 )

• similar body weight at birth but decreased by 50% at P7 and P14

skeleton

increased chondrocyte apoptosis ( J:256718 )

• in tibial growth plates at E18.5 and P14

decreased chondrocyte proliferation ( J:256718 )

• in tibial growth plates at E18.5 and P14

short humerus ( J:256718 )

• at E18.5

short tibia ( J:256718 )

• at E18.5

thin long bone epiphysis ( J:256718 )

• smaller

abnormal cartilage morphology ( J:256718 )

• Safranin-O staining indicates drastically decreased glycosaminoglycan content

• severely reduced chondroitin sulfate content

abnormal long bone epiphyseal plate proliferative zone ( J:256718 )

• drastically disrupted at P14

abnormal long bone hypertrophic chondrocyte zone ( J:256718 )

• drastically disrupted at P14

abnormal chondrocyte morphology ( J:256718 )

• at P14 proliferating chondrocytes in long bones are round and lack the longitudinal organization seen in controls

• some chondrocytes with a flat shape are seen outside the proliferative zone

abnormal endochondral bone ossification ( J:256718 )

• delayed formation of secondary ossification centers

cellular

increased chondrocyte apoptosis ( J:256718 )

• in tibial growth plates at E18.5 and P14

decreased chondrocyte proliferation ( J:256718 )

• in tibial growth plates at E18.5 and P14

limbs/digits/tail

short humerus ( J:256718 )

• at E18.5

short tibia ( J:256718 )

• at E18.5

Genotype
MGI:5487798

cn46

• Allelic Composition: Tg(CAG-cat,-Twist1)1Dbsp/0; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * FVB * SJL

growth/size/body

decreased body size ( J:178268 )

• runted phenotype observed at two weeks of age

decreased body weight ( J:178268 )

• 36-41% reduction in body mass as compared to control

limbs/digits/tail

short limbs ( J:178268 )

• first observed at two weeks of age

• at 8 weeks of age femur and tibia are approximate 14% and 13%, respectively, shorter than controls

skeleton

abnormal long bone epiphyseal plate morphology ( J:178268 )

abnormal long bone epiphyseal plate proliferative zone ( J:178268 )

• tibial growth plates exhibit disorderly columnar arrays of proliferating chondrocytes and acellular regions in the proliferating zone

• atypical vascular invasion and focal regions of bony deposition disrupt contiguous columns of chrondocytes

increased width of hypertrophic chondrocyte zone ( J:178268 )

• width of the tibial growth plate hypertrophic zone is enlarged in four and eight week old mice

decreased trabecular bone volume ( J:178268 )

• decrease in trabecular bone volume fraction is observed in transgenic mice at 4 and 8 weeks

decreased bone trabecula number ( J:178268 )

• reduced trabecular number and increased trabecular spacing

decreased trabecular bone thickness ( J:178268 )

abnormal ossification involved in bone maturation ( J:178268 )

• proportion of cartilage to bone is higher in 2 and 4 week old transgenic mice as compared to controls

Genotype
MGI:6098732

cn47

• Allelic Composition: Gpc6^{tm2c(EUCOMM)Wtsi}/Gpc6^{tm2c(EUCOMM)Wtsi}; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6N * SJL
• Cell Lines: EPD0547_5_C04

growth/size/body

abnormal facial morphology ( J:245694 )

craniofacial

abnormal facial morphology ( J:245694 )

skeleton

abnormal long bone epiphyseal plate proliferative zone ( J:245694 )

• disorganized

decreased length of long bones ( J:245694 )

• mild in newborns, substantial at P15 and P21

Genotype
MGI:5689564

cn48

• Allelic Composition: Runx3^tm3Yg/Runx3^tm3Yg; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

growth/size/body

decreased body height ( J:224290 )

• 2 of 7 mutants exhibit shorter stature

skeleton

skeleton phenotype ( J:224290 , J:243559 )

N • mice show no differences in bone development or structural parameters from wild-type mice (J:224290)

N • do not display scoliosis at 3 months of age (J:243559)

Genotype
MGI:5635889

cn49

• Allelic Composition: Idh1^tm3Mak/Idh1⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:220318 )

• mice that survive after birth die before weaning

prenatal lethality, incomplete penetrance ( J:220318 )

• pups are rarely found alive after birth

growth/size/body

pectus excavatum ( J:220318 )

• pectus excavatum characterized by a caved-in or sunken appearance of the chest and dysplasia of tracheal cartilage

decreased body size ( J:220318 )

• dwarfism

respiratory system

abnormal tracheal cartilage morphology ( J:220318 )

• dysplasia of tracheal cartilage

skeleton

abnormal cartilage morphology ( J:220318 )

• cartilaginous dysplasia of the long bones, ribs, and tracheal cartilage

abnormal tracheal cartilage morphology ( J:220318 )

• dysplasia of tracheal cartilage

abnormal long bone epiphyseal plate morphology ( J:220318 )

• disruption of columnar structure of proliferative chondrocytes, especially in the middle of the growth plate

abnormal cartilage development ( J:220318 )

• tibia shows reduced cartilage mineralization

Genotype
MGI:5582463

cn50

• Allelic Composition: Runx2^tm1Javed/Runx2^tm1Javed; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:212896 )

• mice die within a few minutes of birth due to respiratory failure

skeleton

abnormal craniofacial bone morphology ( J:212896 )

• some elements are undetectable or poorly developed

abnormal limb bone morphology ( J:212896 )

• short

absent metacarpal bones ( J:212896 )

abnormal metatarsal bone morphology ( J:212896 )

• absent

abnormal long bone epiphyseal plate morphology ( J:212896 )

• absent at E18.0 with a lack of hypertrophic chondrocytes and vasculature or blood cells in the mid-diaphyseal region of the femur

absent scapula ( J:212896 )

abnormal pelvic girdle bone morphology ( J:212896 )

• absent

short ribs ( J:212896 )

absent vertebrae ( J:212896 )

growth/size/body

decreased birth body size ( J:212896 )

decreased birth weight ( J:212896 )

respiratory system

respiratory failure ( J:212896 )

• in neonates

craniofacial

abnormal craniofacial bone morphology ( J:212896 )

• some elements are undetectable or poorly developed

limbs/digits/tail

abnormal limb bone morphology ( J:212896 )

• short

absent metacarpal bones ( J:212896 )

abnormal metatarsal bone morphology ( J:212896 )

• absent

Genotype
MGI:5532835

cn51

• Allelic Composition: Mapk14^tm1.2Otsu/Mapk14^tm1.2Otsu; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

skeleton

short femur ( J:204227 )

♂ • at 6 months in male mice

short tibia ( J:204227 )

♂ • at 6 months in male mice

abnormal long bone epiphyseal plate proliferative zone ( J:204227 )

♂ • narrow in male mice

decreased width of hypertrophic chondrocyte zone ( J:204227 )

♂ • in male mice

decreased long bone epiphyseal plate size ( J:204227 )

♂ • in male mice

kyphosis ( J:204227 )

♂ • exaggerated in male mice at 6 months

small vertebrae ( J:204227 )

♂ • short at 6 months in male mice

growth/size/body

decreased body size ( J:204227 )

• by 3 to 4 weeks in female and male mice

decreased body length ( J:204227 )

• in male and female mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:204227 )

N • mice exhibit normal IGF1 serum levels

limbs/digits/tail

short femur ( J:204227 )

♂ • at 6 months in male mice

short tibia ( J:204227 )

♂ • at 6 months in male mice

Genotype
MGI:6466736

cn52

• Allelic Composition: Adamts17^tm1.1Taks/Adamts17^tm1.1Taks; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

skeleton

decreased cranium height ( J:295274 )

• length of the skull is decreased 4-9% at 12 weeks of age

decreased length of long bones ( J:295274 )

• length of the long bones is decreased 4-9% at 12 weeks of age

abnormal vertebrae morphology ( J:295274 )

• length of vertebrae is decreased 4-9% at 12 weeks of age

craniofacial

decreased cranium height ( J:295274 )

• length of the skull is decreased 4-9% at 12 weeks of age

Genotype
MGI:3687745

cn53

• Allelic Composition: Ptch1^tm1Yy/Ptch1^tm1.1Yy; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

skeleton

abnormal osteoblast differentiation ( J:112462 )

• exhibit ectopic osteoblast differentiation in the perichondrium

• exhibit delayed osteoblast maturation as none is seen at E14.5 but is seen at E16.5

increased chondrocyte proliferation ( J:112462 )

• chondrocyte proliferation in the presumed resting zone is significantly increased

abnormal cranium morphology ( J:112462 )

• posterior skull fails to form

abnormal long bone hypertrophic chondrocyte zone ( J:112462 )

• in the humerus, chondrocyte hypertrophy is missing yet osteoblast differentiation occurs at E16.5; chondrocyte hypertrophy does occur in the radius, ulna and tibia

decreased length of long bones ( J:112462 )

• long bones in the limb are shorter

fused synovial joints ( J:112462 )

• exhibit mild synovial joint fusion in embryos, such as the fusion of the radius and ulna with the carpel bones

abnormal bone ossification ( J:112462 )

• exhibit extensive and ectopic ossification at joints

abnormal bone mineralization ( J:112462 )

• bone mineralization is enhanced

• mineralized periosteum extends ectopically to the joint region where mineralization is never seen in wild-type

craniofacial

abnormal cranium morphology ( J:112462 )

• posterior skull fails to form

cellular

abnormal osteoblast differentiation ( J:112462 )

• exhibit ectopic osteoblast differentiation in the perichondrium

• exhibit delayed osteoblast maturation as none is seen at E14.5 but is seen at E16.5

increased chondrocyte proliferation ( J:112462 )

• chondrocyte proliferation in the presumed resting zone is significantly increased

Genotype
MGI:5297172

cn54

• Allelic Composition: Tg(CAG-mRFP1,-SOX9,-EGFP)1Haak/0; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL/6 * SJL

skeleton

abnormal endochondral bone ossification ( J:176952 )

• delay in formation of primary ossification centers in forelimb skeletal elements is observed in E17.5 embryos

abnormal chondrocyte physiology ( J:176952 )

• delayed hypertrophic conversion of proliferating chondrocytes is seen in E15.5 embryos

limbs/digits/tail

abnormal forelimb morphology ( J:176952 )

• an expansion of the hypertrophic zone of in forelimb skeletal elements in observed in E17.5 embryos

Genotype
MGI:5466672

cn55

• Allelic Composition: Sp7^tm1Rnis/Sp7^tm1Rnis; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: C57BL * C57BL/6 * CBA/JNCrlj * SJL

Impairment of ossification in various conditional Sp7^tm1Rnis/Sp7^tm1Rnis mice

skeleton

abnormal skeleton development ( J:191589 )

• mice exhibit reduced vascular invasion into cartilage because of insufficient space in non-degraded cartilage tissues indicating disruption in cartilage matric degradation compared to in control mice

• however, mice exhibit normal angiogenesis in the bone collar and apoptosis in hypertrophic chondrocytes

rickets ( J:191589 )

• calcification is inhibited at E17.5 and E18.5

failure of endochondral bone ossification ( J:191589 )

• endochondral ossification stopped at the hypertrophic stage

Genotype
MGI:5532836

tg56

• Allelic Composition: Tg(Col2a1-cre)1Bhr/Tg(Col2a1-cre)1Bhr
• Genetic Background: involves: C57BL/6 * SJL

craniofacial

abnormal cranium morphology ( J:204227 )

• subtle

skeleton

abnormal cranium morphology ( J:204227 )

• subtle