Modeling human craniofacial disorders in laboratory animals Elona Kolpakova Hart Department of Developmental Biology Town ...
<ul><li>Creation of New Knowledge </li></ul><ul><li>Promotion of New Knowledge </li></ul><ul><li>Development of Analytical...
Potential involvement of kinesin-2 in the Oral-Facial-Digital syndrome
Cleft lip/palate defects in OFD patients and kinesin-2 knockout mouse model kinesin-2 KO  control  OFD syndrome OFD  –  O ...
Oral cavity defects in OFD patients and kinesin-2 knockout mouse model tongue mandible (lower jaw) OFD syndrome  kinesin-2...
Tongue abnormalities observed in patients with OFD and kinesin 2-deficient mice OFD patient  kinesin-2 knockout mouse
Extra-digits found in OFD patients and kinesin-2 model mouse OFD syndrome  kinesin-2 knockout  normal mouse mouse
Translating knowledge into diagnostics and treatments <ul><li>Identification of a candidate gene involved in a human </li>...
The role of Polycystins in  human skeletal development
Impaired postnatal growth of the rostrum in the  Polycystin-1  and  Polycystin-2  KO mice
Cranial base defects in polycystin-1 and polycystin-2 knockout mice control  polycystin-2 KO  control  polycystin-2 KO
Skull Abnormalities in Metaphyseal Chondrodysplasia Type Jansen There are similarities between skull defects in polycystin...
Long Bone Defects in Metaphyseal Chondrodysplasia Type Jansens <ul><li>Delayed irregular ossification </li></ul><ul><li>Ge...
Increased trabecular bone volume and bone marrow fibrosis in Jansen’s chondrodysplasia mouse model and polycystin-2 defici...
Working Hypothesis Parathyroid   Hormone - and  Polycystin -mediated regulatory pathways interact in regulating bone forma...
Modeling orthodontic procedures in animals
New bone formation in response to  mid-palatal suture expansion in mice old bone   new bone Hou  et al.,   Polycystic kidn...
Harvard Medical School Harvard School of Dental Medicine Jing Zhou, BWH Nicolas Brady, HSPH Joe Gleeson, UCSD Kimberly Wu ...
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Town Hall Meeting, Harvard Dental School, 10/21/2009

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Modeling Human Skeletal Disorders in Animals

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Town Hall Meeting, Harvard Dental School, 10/21/2009

  1. 1. Modeling human craniofacial disorders in laboratory animals Elona Kolpakova Hart Department of Developmental Biology Town Meeting 10/21/2009
  2. 2. <ul><li>Creation of New Knowledge </li></ul><ul><li>Promotion of New Knowledge </li></ul><ul><li>Development of Analytical skills </li></ul>EDUCATION PROCESS Institutional Research in Medical and Dental Education
  3. 3. Potential involvement of kinesin-2 in the Oral-Facial-Digital syndrome
  4. 4. Cleft lip/palate defects in OFD patients and kinesin-2 knockout mouse model kinesin-2 KO control OFD syndrome OFD – O ral- F acial- D igital syndrome
  5. 5. Oral cavity defects in OFD patients and kinesin-2 knockout mouse model tongue mandible (lower jaw) OFD syndrome kinesin-2 KO mouse control kinesin-2 KO
  6. 6. Tongue abnormalities observed in patients with OFD and kinesin 2-deficient mice OFD patient kinesin-2 knockout mouse
  7. 7. Extra-digits found in OFD patients and kinesin-2 model mouse OFD syndrome kinesin-2 knockout normal mouse mouse
  8. 8. Translating knowledge into diagnostics and treatments <ul><li>Identification of a candidate gene involved in a human </li></ul><ul><li>syndrome/disease </li></ul><ul><li>Detection of causative mutation(s) in the candidate gene in collaboration with patients and medical professionals </li></ul><ul><li>Development of diagnostic tests and potential treatments </li></ul>
  9. 9. The role of Polycystins in human skeletal development
  10. 10. Impaired postnatal growth of the rostrum in the Polycystin-1 and Polycystin-2 KO mice
  11. 11. Cranial base defects in polycystin-1 and polycystin-2 knockout mice control polycystin-2 KO control polycystin-2 KO
  12. 12. Skull Abnormalities in Metaphyseal Chondrodysplasia Type Jansen There are similarities between skull defects in polycystin-deficient mice and patients with Jansen’s Metaphyseal chondroplasia Holthusen W. et al., Pediatric Radiology, 1975
  13. 13. Long Bone Defects in Metaphyseal Chondrodysplasia Type Jansens <ul><li>Delayed irregular ossification </li></ul><ul><li>Generalized symmetric shortening of long bones </li></ul><ul><li>Deeply-cupped metaphyseal ends of long bones </li></ul><ul><li>Ossified shafts of long bones </li></ul>control polycystin-2 KO
  14. 14. Increased trabecular bone volume and bone marrow fibrosis in Jansen’s chondrodysplasia mouse model and polycystin-2 deficient mice control Jansen’s control Jansen’s Calvi L.M. et al, JCI, 2001 control polycystin-2 knockout control polycystin-2 knockout
  15. 15. Working Hypothesis Parathyroid Hormone - and Polycystin -mediated regulatory pathways interact in regulating bone formation and growth What is the molecular mechanism? New Genes = New Potential Drug Targets
  16. 16. Modeling orthodontic procedures in animals
  17. 17. New bone formation in response to mid-palatal suture expansion in mice old bone new bone Hou et al., Polycystic kidney disease 1 (Pkd1) gene is required for the responses of osteochondroprogenitor cells to midpalatal suture expansion in mice. 2009, Bone Control Experiment
  18. 18. Harvard Medical School Harvard School of Dental Medicine Jing Zhou, BWH Nicolas Brady, HSPH Joe Gleeson, UCSD Kimberly Wu Kimberly Whippy Vikrum Nanda Bo Hou Bjorn R. Olsen Lab

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