BAG3 null mutation mice show severe striated muscle degeneration and early lethality, characterized by myofibrillar myopathy [16].
Remarkably, lde/lde rats displayed phenotypic characteristics similar to Wwox KO mice including severe dwarfism and early lethality.
Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects.
Furthermore, they indicate that phosphorylation at this residue is not functionally involved in those APP-mediated functions that prevent (NMJ) defects and early lethality in APLP2 null mice.
Mice with the most common human Gaucher disease mutations, N370S and L444P, have early lethality [8], [28], and thus, are not available for these studies.
One possible mechanism that has been suggested to explain the etiology of early lethality in XO embryos is the presence of imprinted genes on the X chromosmes [5].
Two out of the four groups which contain 70% of the total number of samples demonstrate early lethality in XO embryos even before mature embryonic tissues are visible.
However, because of early lethality of complete loss of signaling models, it was difficult to assess their requirements postnatally during homeostasis.
Thus no conclusion about the most prevalent phenotype of the 45,XO karyotype, namely the early lethality, can be reached by studying these patients.
However, generation of iPS from Turner's syndrome patients might not advance our understanding on the early lethality, since the patients are the exceptional cases that survived to term.
The most common explanation for the early lethality of XO embryos is a haploinsufficiency effect of pseudoautosomal genes on the X chromosome.
