Over the last year we have been studying a very interesting genetic model
We call them “TRIBBLES”………
TRIB1 (Tribbles Pseudokinase 1) is a protein containing a serine/threonine kinase-like domain and is expressed in skeletal muscle, thyroid, pancreas, peripheral blood leukocytes, and bone marrow.
In mice, Trib1 is critical for the differentiation of tissue-resident macrophages and in musculoskeletal tissues it is highly expressed in the bone marrow of adult humans.
Mice overexpressing Trib1 in cartilage (left) are much smaller than the wild type litter mates (right) and present with a pronounced hip dysplasia. The bones appear dense, shorter and broader and are very reminiscent of osteopetrosis.
Fantastic image generated by Jennifer Gerbracht who is currently an Erasmus student in the lab. Bone mineral content quantification by Faxitron X-ray microradiography. The knee joint of a wild type mouse (left) is shown compared to a mutant TRIBBLE mouse with much higher bone density (right and shown in red).
An excellent programme that features the best in rare skeletal disease clinical practice and research, including:-
Bone and osteocyte biology: lessons from human genetic diseases
Brendan Lee (Houston, USA)
Classic osteogenesis imperfecta
Nick Shaw (Birmingham, UK)
Recessive osteogenesis imperfecta
Frank Rauch (Montreal, Canada)
Shared therapeutic targets in genetic skeletal diseases
Mike Briggs (Newcastle upon Tyne, UK)
New insights into genetic defects of bone and cartilage
Ekkehart Lausch (Freiburg, Germany)
Achondroplasia – new therapy
Laurence Legeai-Mallet (Paris France)
Full Programme here ICCBH programme – printable
The utility of mouse models to provide information regarding the pathomolecular mechanisms in human genetic skeletal diseases: The emerging role of endoplasmic reticulum stress.
Available as open access here