Several larger animal models of dystrophin deficiency have more severe phenotypes, although a variety of limitations remains.
Because longer tracts cause more severe phenotypes, contracting them may provide a therapeutic avenue.
Alleles that fail to transcribe the mutated gene do not exhibit transcriptional adaptation, and these alleles give rise to more severe phenotypes than alleles displaying mutant mRNA decay.
Correspondingly, carriers of 1.7 Mb BP1-BP5 rearrangementhathat encompass both the BP2-BP3 and BP4-BP5 loci showed more severe phenotypes.
Some patients showed more severe phenotypes and carry the clinical diagnosis of Fryns syndrome.
Finally, Fringe perturbations result in more severe phenotypes than those previously reported for Notch dominant-negative (LvN neg)) injections or reported here for Notch MO (NMO) injections.
However, hCLP46−/− embryos show more severe phenotypes compared to those displayed by other global regulators of canonical Notch signaling, suggesting that hCLP46 is likely to have additional important targets during mammalian development (Fernandez-Valdivia et al., 2011).
However, some Asxl2−/− embryos died in utero and could have more severe phenotypes than the ones that were born.
For example we consistently found more severe phenotypes in the posterior hemisphere of the eye when expressing an RNAi transgene.
However, more severe phenotypes including osteopetrosis in these mice have also been observed, suggesting the existence of alternative factor(s) sharing the same receptor [18].
However, it must be mentioned that more severe phenotypes were observed in unrelated families carrying the heterozygous mutations G1408R, T220I, or DelF1617 (Table 3) [32], [33], [33].
