Table 1.
Cre-recombinase expressing mouse strains used for targeting mutant ACVR1
| Transgenic strain |
Lineages targeted | Temporal expression |
Phenotype | Compound heterozygotes/live births |
HO/n tested |
|---|---|---|---|---|---|
| Pax7-Cre (57) | Satellite cell; Myoblast; Myofiber |
Embryonal – maturity |
Embryonal lethality | 0/>30 | − |
|
Pax7-CreERT2
(57) |
Satellite cell | Inducible (tamoxifen) |
No spontaneous or injury- induced HO |
Mendelian | 0/10 |
| Myf6-Cre (56) | Myofiber and late myoprogenitor |
Embryonal – maturity |
No spontaneous or injury- induced HO |
Mendelian | 0/10 |
|
SM-MHC-Cre
(51) |
Vascular smooth muscle |
Embryonal – maturity |
Embryonal lethality | 0/>30 | − |
|
SM22α-Cre
(55) |
Vascular smooth muscle; Pericyte subset |
Embryonal – maturity |
No spontaneous or injury- induced HO |
Mendelian | 0/13 |
| Tie2-Cre (59) | Vascular endothelium; Myeloid subset; circulating endothelial progenitor |
Embryonal – maturity |
Embryonal lethality | 0/>25 | − |
|
Cadh5- CreERT2 (58) |
VE-Cadherin expressing mature endothelial cells |
Inducible (tamoxifen) |
No spontaneous or injury- induced HO |
Mendelian | 0/11 |
|
Cspg4- CreERT2 (52) |
NG2-expressing pericytes |
Inducible (tamoxifen) |
No spontaneous or injury- induced HO |
Mendelian | 0/17 |
| Vav1-Cre (24) | Bone marrow hematopoietic and endothelial |
Embryonal – maturity |
No spontaneous or injury- induced HO |
Mendelian | 0/14 |
| Mx1-Cre (50) | Bone marrow; spleen; thymus; liver |
Inducible (pIpC) |
Injury-induced intramuscular HO |
Mendelian | 0/20 −CTX; >30/30 +CTX |
| Scx-Cre (20) | Tendon progenitor cells |
Embryonal – maturity |
Spontaneous joint
and ligament HO |
Mendelian | >30/30 |
Various tissue promoter-specific Cre-expressing mouse strains were mated with homozygous ACVR1Q207D-Tg/Q207D-Tg mice and tested for the capacity to generate live compound transgenic or compound knock-in and transgenic offspring. No live compound mutant mice were produced as a result of mating ACVR1Q207D-Tg/Q207D-Tg mice with Pax7-Cre, SM-MHC-Cre, or Tie2-Cre strains among the stated number of live births per mating strategy. In matings with Myf6-Cre, SM22α-Cre, and Vav1-Cre, compound mutant mice were produced in expected Mendelian ratios, however, no spontaneous HO was observed in a minimum of 10 live compound mutants when observed for up to 16 weeks of age, nor did any HO occur with intramuscular cardiotoxin injection at P10-P14 in a minimum of 5 injected compound mutants. When offspring of ACVR1Q207D-Tg/Q207D-Tg and Pax7-CreERT2 or Cadh5-CreERT2, Cspg4-CreERT2 matings were injected with tamoxifen (50 mg/kg i.p daily P14-P21), high efficiency recombination was observed among sublaminar satellite cells and vascular endothelial cells, respectively. However, no spontaneous or cardiotoxin-induced HO was observed among a minimum of 10 compound mutant mice following tamoxifen injection, and observation up to 16 weeks of age.