Table 3.
Summary of phenotypes with loss of function in mouse of Pax3, Pax7, Myf5, MyoD, Myogenin, Mrf4, and combinations of Pax3, Pax7 and MRFs. It should be noted that some Myf5 null and Mrf4 null alleles affected the expression of Mrf4 and Myf5, respectively. Thus, for instance, the Myf5nlacZ/nlacZ mice, originally described as Myf5 null mice (Tajbakhsh et al., 1997), are also null for Mrf4 (Kassar-Duchossoy et al., 2004). Only the Myf5loxP/loxP allele leaves Mrf4 intact (Kassar-Duchossoy et al., 2004). In this table phenotypes described for both Myf5 null and compound Myf5 and MyoD null are based on Myf5loxP/loxP mice. Similarly, while three Mrf4 null alleles were generated (Braun and Arnold, 1995; Patapoutian et al., 1995; Zhang et al., 1995), only one Mrf4 null allele leaves Myf5 intact (Olson et al., 1996; Zhang et al., 1995). The phenotype described here for the Mrf4 null is based on this allele from the Olson lab (Zhang et al., 1995).
| Pax3 (Lepper et al., 2009; Relaix et al., 2004 and references therein) |
Pax7 (Kuang et al., 2006; Lepper et al., 2009; Oustanina et al., 2004; Relaix et al., 2006; Seale et al., 2000) |
Pax3/ Pax7 (Relaix et al., 2005) |
Pax3/ Myf5/ Mrf4 (Tajbakhsh et al., 1997) |
Myf5 (Gayraud- Morel et al., 2007; Kassar- Duchossoy et al., 2004) |
MyoD (Gayraud- Morel et al., 2007; Kablar et al., 1997; Megeney et al., 1996; Rudnicki et al., 1992; White et al., 2000; Yablonka- Reuveni et al., 1999) |
Mrf4 (Zhang et al., 1995) |
Myogenin or Myogenin/Myf5 or Myogenin/Myo D or Myogenin/Mrf4 (Hasty et al., 1993; Nabeshima et al., 1993; Rawls et al., 1995; Rawls et al., 1998; Venuti et al., 1995) |
Myf5/ MyoD (Kassar- Duchossoy et al., 2004; Kassar- Duchossoy et al., 2005) |
Myf5/ Mrf4 (Braun and Arnold, 1995; Kassar- Duchossoy et al., 2004; Tajbakhsh et al., 1997) |
MyoD/ Mrf4 (Rawls et al., 1998) |
Myf5/ MyoD/ Mrf4 (Kassar- Duchossoy et al., 2004; Rudnicki et al., 1993) |
MyoD/Mrf4/ Myogenin (Valdez et al., 2000) |
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Axial | Defects in somite segmentation, epaxial and hypaxial dermo-myotome, trunk muscle | No phenotype observed | Only form primary myotome. No embryonic or fetal axial muscle. | Defective primary myotome. No embryonic or fetal axial muscle | Delay of primary myotome formation, lack of some epaxial muscles in adult. | Normal primary myotome and epaxial muscles, delay in hypaxial muscles | No phenotype observed | Embryonic axial muscle normal, no MyHCperi+ fetal axial muscle | Delay of primary myotome, embryonic axial muscle at E12.5, no fetal axial muscle | Delayed primary myotome, lack of some epaxial muscle | Embryonic axial muscle normal, no axial fetal muscle | No myotome or axial muscle | Only Myf5+ myoblasts, no myofibers |
| Embryonic Limb E11.5–E14.5 | No limb muscle due to defects in delamination, migration, maintenance of limb progenitors | No phenotype observed | No limb muscle (see Pax3 phenotype) | No limb muscle (see Pax3 phenotype) | No phenotype observed | 2.5 day delay in limb myogenesis, no limb muscle until E13.5 | No phenotype observed | Normal embryonic limb myoblasts and MyHCemb+ myofibers | No limb muscle at E12.5 (MyoD phenotype), a few myofibers at E14.5 | No phenotype observed | Normal embryonic limb myoblasts and myofibers | No limb muscle | Not explicitly tested |
| Fetal Limb E14.5–E18.5 | No limb muscle (see above) | No phenotype observed | No limb muscle (see Pax3 phenotype) | No limb muscle (see Pax3 phenotype) | No phenotype observed | No phenotype observed | No phenotype observed | No MyHCperi+ fetal limb myofibers, a few residual myofibers, myoblasts present | Few myofibers at E14.5, no fetal myofibers by birth | No phenotype observed | Myoblasts present, but few residual myofibers | No limb muscle | No differentiated myofibers, no MyHCemb |
| Neonatal Limb P0–P21 | Dead | Defects in satellite cell survival, proliferation, and differentiation (as tested by conditional deletion) | Dead | Dead | No phenotype observed | No phenotype observed | No phenotype observed | Few residual myofibers, perinatal death | No muscle at birth, perinatal death | No phenotype observed, perinatal death | Few residual myofibers, perinatal death | No limb muscle, perinatal death | No differentiated myofibers, no MyHCemb, perinatal death |
| Adult/Regeneration | Dead (Pax3 null mice) Not required (as tested by conditional deletion) | No effect on adult muscle regeneration (as tested by conditional deletion) | Dead | Dead | Impaired regeneration with delayed differentiation, fiber hypertrophy, increased fat and fibrosis | Delayed and impaired regeneration with increased number of satellite cells and fewer differentiated myofibers | Not explicitly tested | Dead | Dead | Dead | Dead | Dead | Dead |