Estrogen pretreatment modulates morphine-induced conditioned place preference in ovariectomized mice

Estrogen is known to modulate the neurotransmission in the brain. The main aim of this study was to investigate the effects of estrogen on the rewarding properties of morphine using conditioned place preference (CPP) paradigm in adult female mice. The possible rewarding effect of estrogen was also examined in ovariectomized mice. Following a 6-day conditioning procedure, sham operated animals showed a significant preference towards the side previously paired with a range of morphine doses (2, 5 and 10—but not 20—mg/kg, SC). However, ovariectomized mice showed decreased CPP compared to gonadally intact mice with a right shift in their morphine dose-response curve. These effects were reversed by chronic daily administration of estradiol benzoate (EB; 20 µg/kg, SC). Furthermore, in ovariectomized mice, EB per se was able to induce CPP. In conclusion, our findings indicate that estradiol has a facilitating effect on morphine reward while its deficiency increases the threshold dose of morphine to induce CPP.     

Genome‐wide single nucleotide polymorphism‐based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome‐wide single nucleotide polymorphism (SNP) array‐based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB‐targeted next‐generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed genetically.