All Phenotypes Tg(Col2a1-rtTA,tetO-COMP*)2Jath MGI Mouse

increased chondrocyte apoptosis ( J:233238 )

• doxycline exposure in the prenatal period to P7 evokes very little growth plate chondrocyte death, however doxycycline exposure in the prenatal period to P14, P21 or P28, increases growth plate chondrocyte death

abnormal skeleton morphology ( J:233238 )

• doxycycline treated mice show a reduction in the size of the skeleton by P7 and are 12% shorter at P28, at which time it is most marked

decreased cranium length ( J:233238 )

• total skull length is reduced by 10% in doxycycline treated mice

• however, intercanthal distance is normal

abnormal spine curvature ( J:233238 )

• exaggerated curvature in the thoracic and lumbar spine is seen in most doxycycline treated mice by P28

abnormal epiphyseal plate morphology ( J:233238 )

• doxycline exposure in the prenatal period to P14, P21, or P28 increases growth plate chondrocyte death and doxycline exposure to P21 or P28 results in increased inflammation in the growth plate

• treatment with lithium reduces pup viability and disrupts growth plate organization

• treatment of doxycycline-administered mice with valproate reduces apoptosis by about 50% and improves growth plate architecture, however skull and limb lengths are reduced by another 9%

• treatment of doxycycline-administered mice with phenylbutyric acid only minimally reduces apoptosis in the growth plate

abnormal long bone epiphyseal plate morphology ( J:152756 )

• doxycycline-treated mice exhibit fewer hypertrophic chondrocytes compared with wild-type mice

• doxycycline-treated mice exhibit retention of extracellular matrix protein and intracellular matrix formation in the ribosomal endoplasmic reticulum cisternae in the growth plate unlike in wild-type mice

disorganized long bone epiphyseal plate ( J:152756 )

• in doxycycline-treated mice

abnormal chondrocyte physiology ( J:152756 )

• doxycycline-treated mice exhibit an increase in apoptosis in the growth plate compared to in wild-type mice

increased chondrocyte apoptosis ( J:233238 )

• doxycline exposure in the prenatal period to P7 evokes very little growth plate chondrocyte death, however doxycycline exposure in the prenatal period to P14, P21 or P28, increases growth plate chondrocyte death

decreased cranium length ( J:233238 )

• total skull length is reduced by 10% in doxycycline treated mice

• however, intercanthal distance is normal

abnormal snout morphology ( J:233238 )

• an increase in cartilage is seen in the snout of P21 and P28 doxycycline treated mice

short snout ( J:233238 )

• total snout length is reduced by 15% in doxycycline treated mice

abnormal snout morphology ( J:233238 )

• an increase in cartilage is seen in the snout of P21 and P28 doxycycline treated mice

short snout ( J:233238 )

• total snout length is reduced by 15% in doxycycline treated mice

pectus carinatum ( J:233238 )

• doxycycline treated mice show a marked progression in the development of pectus carinatum at P28

increased inflammatory response ( J:233238 )

• inflammation as analyzed by markers develops in the growth plate when mice are exposed to doxycycline from conception to P21 or P28, but not when they are only exposed to it to E15.5, P1, P7 or P14

• exercise in doxycycline treated mice exacerbates inflammation in the articular cartilage

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

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pseudoachondroplasia		DOID:0080047	OMIM:177170	J:152756 , J:233238

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