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Transgenic Mice with Conditionally-Enhanced Bone Morphogen Protein (BMP) Signaling: A Model for Human Bone Diseases

Posted Jun 15 2010 5:00pm

Description of Invention:
This technology relates to novel animal models of several human bone diseases that have been linked to enhanced BMP signaling. More specifically, this mouse model expresses a mutant receptor for BMP, known as Alk2 that is always actively signaling. This receptor is under the control of the Cre-loxP system, which allows control of expression of the mutant Alk2 in both a developmental and tissue-specific manner. As a result, the enhanced signaling conditions exhibited in multiple human bone-related diseases can be studied with the same animals.

The mouse model can be applied to the study of BMP signaling-related human diseases such as fibrodysplasia ossificans progressiva, which involves the postnatal transformation of connective tissue into bone. Another example of BMP signaling-related disease is Craniosynostosis, which involves the premature closing of the sutures in childhood so that normal brain and skull growth are inhibited. This mouse model can potentially be used in other human diseases where BMP signaling might play a pivotal role, for example cleft lip and cleft palate, breast cancer, osteoarthritis, lung fibrosis, multiple myeloma, juvenile polyposis, cephalic neural tube closure detects, diabetes and other types of blood glucose control problems, and pulmonary hypertension.

Development Status:
Early-stage development.

Yuji Mishina (NIEHS)
Manas K Ray (NIEHS)
Gregory J Scott (NIEHS)

Patent Status:
Research Material -- patent protection is not being pursued for this technology

Relevant Publication:
  1. T Fukada et al. Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2. Genesis. 2006;44:159-167.
  2. L Kan et al. Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype. Am J Path. 2004 Oct;165(4):1107-1115. [ PubMed abs ]
  3. EM Shore et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressive. Nat Genet. 2006 May;38(5):525-527. [ PubMed abs ]

Licensing Status:
Available for non-exclusive licensing.

Internal Medicine
Internal Medicine - Research Materials
Animal Model

For Additional Information Please Contact:
Steven Standley Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-4074
Fax: 301-402-0220

Ref No: 1831

Updated: 06/2010

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