Phenotypes Associated with This Genotype

Genotype
MGI:4429125

• 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

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

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