Thanks to generous sponsorship from La Jolla Pharmaceutical Company, the IFOPA now owns a conditional ALK2R206H FOP mouse model that can be distributed to academic and corporate labs for unrestricted research use. The new mouse design was created in collaboration with Drs. Dan Perrien (Vanderbilt University), Aris Economides (Regeneron), Yuji Mishina (University of Michigan), Maurizio Pacifici (Children's Hospital of Philadelphia) and Eileen Shore (University of Pennsylvania). The mice are housed at Vanderbilt University Medical Center, by Dr. Dan Perrien, on behalf of the IFOPA. The IFOPA is very grateful to Dr. Perrien for his time and support to maintain this mouse colony.
Like other mouse models of FOP, a conditional ALK2R206H construct was knocked in to the endogenous Alk2 gene immediately following intron 4. However, this model incorporates both lox and rox recombination sites so that cre or dre recombinases can be used to excise murine Alk2 Exons 5-10 and induce expression of the corresponding exons of human ALK2R206H and an eGFP marker. One limitation of cre-lox inducible disease models is that they limit the use of cre-lox to study other genes and pathways of importance in FOP. To address this limitation, one of the lox5171 sites can be removed by Flp recombinase, rendering the engineered Alk2 gene insensitive to cre and enabling independent control of ALK2R206H expression by dre and recombination of other floxed genes of interest with cre. Both cre- and dre-inducible lines are available for distribution. FOP mice crossed with cre or dre expressing lines (e.g. R26creERt2) may be available depending on IP/licensing restrictions of the parental lines and current use in Dr. Perrien’s lab.
Phenotyping of the model is ongoing. At this time, Dr. Perrien’s lab has confirmed that these mice form robust intramuscular HO following CTX or pinch injury of the hindlimbs that is similar in severity and timeline to the ALK2R206H-FlEx model (Hatsell et al. Sci Trans Med 2015). Additional, up-to-date information on the phenotype, construct, or other information are available upon request from Dr. Dan Perrien.
To request mice, please complete the FOP Mouse Model Request form. Once approved, you will be required to complete a Uniform Biological Material Transfer Agreement (UBMTA). Transfer will be coordinated by the Vanderbilt University Medical Center (VUMC) Department of Animal Care via the Perrien lab. All shipping and veterinary testing expenses are to be paid by the requesting laboratory.