Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum.
Here, we show that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to I1061TNPC1 corrects the localization/maturation defect of the mutant protein.
Inactivating mutations in the GALT-II gene (B3GALT6) associated with Ehlers-Danlos syndrome cause proteoglycan maturation defects similar to FAM20B deletion.
Inactivating mutations in the GALT-II gene (B3GALT6) associated with Ehlers-Danlos syndrome cause proteoglycan maturation defects similar to FAM20B deletion.
Inactivating mutations in the GALT-II gene (B3GALT6) associated with Ehlers-Danlos syndrome cause proteoglycan maturation defects similar to FAM20B deletion.
Both mislocalization and misfolding of mutant neutrophil elastase protein resulting in ER stress and subsequent induction of the unfolded protein response (UPR) have been proposed to be responsible for neutrophil survival and maturation defects.
Further, this study was able to demonstrate for the first time in vivo that the severity of the uromodulinmaturation defect as well as onset and speed of progression of renal dysfunction and morphological alterations are strongly dependent on the particular Umod mutation itself and the zygosity status.
Interestingly, the overall abnormal features displayed by the SRC-1(+/-)/TIF2(-/-) and SRC-1(-/-)/TIF2(-/-) mutant testes, including spermatid maturation defects, increase in Sertoli cell lipid stores, loss of immature germ cells, and formation of giant multinucleated spermatids, are commonly detected in testes of elderly men, suggesting that deficiencies in molecular pathways involving TIF2 and SRC-1 in Sertoli cells could participate in testicular senescence.
An accurate quantification of testicular mRNA levels of genes expressed in spermatogonia was carried out by RT-qPCR in individuals showing SpF owing to germ cell maturation defects, Sertoli cell-only syndrome or conserved spermatogenesis.
The analysis of our patients' sample, carrying point mutations or complex rearrangements in DMD gene, contributes to the knowledge on phenotypic correlations in dystrophinopatic patients and can provide a better understanding of pre-mRNA maturation defects and dystrophin functional domains.
In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects.
The recently identified zebrafish <i>gfi1aa</i> gene trap allele <i>qmc551</i> drives erythroid green fluorescent protein (GFP) instead of Gfi1aa expression, yet homozygous carriers have normal prRBCs. prRBCs display a maturation defect only after splice morpholino-mediated knockdown of Gfi1b in <i>gfi1aa</i><sup>
The maturation defect is accompanied by failure to form an enveloping IMC and a marked swelling of the digestive vacuole, suggesting PhIL1 and PIP1 are required for correct membrane trafficking.
Interestingly, the overall abnormal features displayed by the SRC-1(+/-)/TIF2(-/-) and SRC-1(-/-)/TIF2(-/-) mutant testes, including spermatid maturation defects, increase in Sertoli cell lipid stores, loss of immature germ cells, and formation of giant multinucleated spermatids, are commonly detected in testes of elderly men, suggesting that deficiencies in molecular pathways involving TIF2 and SRC-1 in Sertoli cells could participate in testicular senescence.
Moreover, this study identifies Tlk2, Utx, Gpr64, Sult4a1, Rap2ip, Vstm2 and HoxA10 as possible Mll5 targets that together may account for the observed spermatozoa maturation defects.