Sci. Aging Knowl. Environ., 15 December 2004
Vol. 2004, Issue 50, p. tg6
GENETICALLY ALTERED MICE
||129/Ola, C57Bl/6, FVB/N
||1. Gdf5 (growth differentiation factor 5; also bp, brachypodism; or cartilage-derived morphogenetic protein-1, CDMP-1)
2. Bmpr1a (bone morphogenetic protein receptor, type 1a; also ALK3, Bmpr, or BMPR-IA)
|Type of change
||Because Bmpr1a-null mice die during embryogenesis, a Gdf5-Cre/loxP system was used to regulate the expression of Bmpr1a. In this system, the Bmpr1a gene is deleted late in embryogenesis specifically in tissues that will eventually develop into joints.
|Nature of protein
||Gdf5 encodes a member of the bone morphogenetic protein (BMP) family of proteins, which are secreted signaling molecules implicated in skeletal development. Expression of Gdf5 is primarily restricted to regions where joints develop.
Bmpr1a encodes a transmembrane BMP receptor. In limbs, Bmpr1a is expressed in cells and tissues associated with joint formation and in interdigital limb mesenchyme.
||Gdf5-Cre/Bmpr1afloxP mice can bypass the embryonic lethality seen in Bmpr1a-null animals and survive to adulthood. However, the Gdf5-Cre/Bmpr1afloxP mice exhibit a number of defects, including shortened ears, webbing between the first and second digits of the feet, and reduced or entirely missing cartilage in the joints.
The Gdf5-Cre/BmpR1afloxP mice provide an appropriate model for the study of osteoarthritis because the articular cartilage within the joints wears away gradually in a fashion similar to that seen in human osteoarthritis (see Loeser Perspective and Shakoor Case Study).
|Corresponding human phenotype
||Germline nonsense mutations in BMPR1A have been associated with juvenile polyposis, an autosomal dominant syndrome in which patients exhibit an increased risk of gastrointestinal cancers.
||R. B. Rountree, M. Schoor, H. Chen, M. E. Marks, V. Harley, Y. Mishina, D. M. Kingsley, BMP receptor signaling is required for postnatal maintenance of articular cartilage. PLoS Biol. 2, e355 (2004).
||These mice are not commercially available. Please contact:
David M. Kingsley
Department of Developmental Biology and Howard Hughes Medical Institute
Stanford University School of Medicine
Stanford, CA 94305-5329
||Mouse Genome Informatics
Online Mendelian Inheritance in Man
bone morphogenetic protein receptor
December 15, 2004
- S. T. Baur, J. J. Mai, S. M. Dymecki, Combinatorial signaling through BMP receptor IB and GDF5: Shaping of the distal mouse limb and the genetics of distal limb diversity. Development 127, 605-619 (2000).[Abstract]
- S. C. Chang, B. Hoang, J. T. Thomas, S. Vukicevic, F. P. Luyten, N. J. Ryba, C. A. Kozak, A. H. Reddi, M. Moos Jr., Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. J. Biol. Chem. 269, 28227-28234 (1994).[Abstract/Free Full Text]
- Y. Mishina, M. C. Hanks, S. Miura, M. D. Tallquist, R. R. Behringer, Generation of Bmpr/Alk3 conditional knockout mice. Genesis 32, 69-72 (2002).[CrossRef][Medline]
- B. A. Roelen, M. J. Goumans, M. A. van Rooijen, C. L. Mummery, Differential expression of BMP receptors in early mouse development. Int. J. Dev. Biol. 41, 541-549 (1997).[Medline]
- R. B. Rountree, M. Schoor, H. Chen, M. E. Marks, V. Harley, Y. Mishina, D. M. Kingsley, BMP receptor signaling is required for postnatal maintenance of articular cartilage. PLoS Biol. 2, e355 (2004).[CrossRef][Medline]
Mice. Sci. Aging Knowl. Environ. 2004
(50), tg6 (2004).