Progesterone is a steroid hormone that is necessary to maintain pregnancy in mammals. We recently found that mice with a conditional deletion of Becn1/Beclin 1 specifically in the progesterone-synthes Show more
Progesterone is a steroid hormone that is necessary to maintain pregnancy in mammals. We recently found that mice with a conditional deletion of Becn1/Beclin 1 specifically in the progesterone-synthesizing cells of the corpus luteum, had reduced progesterone synthesis and these mice failed to maintain pregnancy.(1) Furthermore, we identified that lipid storage and feedback through PRLR (prolactin receptor) and LHCGR (luteinizing hormone/choriogonadotropin receptor) were negatively affected by Becn1 deletion. BECN1 is necessary for the interaction of the 2 catalytic subunits of the class III phosphatidylinositol 3-kinase complex, PIK3C3, and PIK3R4, which are responsible for the generation of phosphatidylinositol 3-phosphate that is required for nucleation of the phagophore. Work from Sun et al. and Itakura et al. demonstrated that this BECN1 complex is also necessary for the fusion of autophagosomes and endosomes with lysosomes. Therefore, we suspected that ablating Becn1 in luteal cells would inhibit macroautophagy, hereafter referred to as autophagy. In support, we provide evidence that autophagic flux is reduced in our model. Thus, this study provides evidence that Becn1 is necessary for steroid production in murine luteal cells. Show less
Abdul Noor, Anath C Lionel, Sarah Cohen-Woods+17 more · 2014 · American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · Wiley · added 2026-04-24
Genome-wide single nucleotide polymorphism (SNP) data from 936 bipolar disorder (BD) individuals and 940 psychiatrically healthy comparison individuals of North European descent were analyzed for copy Show more
Genome-wide single nucleotide polymorphism (SNP) data from 936 bipolar disorder (BD) individuals and 940 psychiatrically healthy comparison individuals of North European descent were analyzed for copy number variation (CNV). Using multiple CNV calling algorithms, and validating using in vitro molecular analyses, we identified CNVs implicating several candidate genes that encode synaptic proteins, such as DLG1, DLG2, DPP6, NRXN1, NRXN2, NRXN3, SHANK2, and EPHA5, as well as the neuronal splicing regulator RBFOX1 (A2BP1), and neuronal cell adhesion molecule CHL1. We have also identified recurrent CNVs on 15q13.3 and 16p11.2-regions previously reported as risk loci for neuropsychiatric disorders. In addition, we performed CNV analysis of individuals from 215 BD trios and identified de novo CNVs involving the NRXN1 and DRD5 genes. Our study provides further evidence of the occasional involvement of genomic mutations in the etiology of BD, however, there is no evidence of an increased burden of CNVs in BD. Further, the identification of CNVs at multiple members of the neurexin gene family in BD individuals, supports the role of synaptic disruption in the etiology of BD. Show less