Identified a new possible cause at the origin of Kallmann’s and Down’s syndromes

Identified a new possible cause at the origin of Kallmann’s and Down’s syndromes

magazine Cell and Developmental Biology publishes a study by the Universities of Milan and Turin and the CNR Naples that paves the way to a new understanding of the causes of serious hereditary diseases such as Kallmann and Down syndrome, characterized by male and female infertility (hypogonadism), absence or reduced awareness smell (anosmia) and other developmental disorders.

The study titled Anosmin-1-like effect of UMODL1/olfactorin on chemomigration of mouse GnRH neurons and development of zebrafish olfactory axonsis specifically inserted in the area Studies on the origin of fertility loss in people with syndromic diseases and was born from the collaboration between the Departments of Pharmaceutical Sciences and Pharmacological and Biomolecular Sciences of the University of Milan, the Department of Molecular Biotechnologies and Health Sciences of the University of Turin and the Institute of Life Sciences and Bioresources of the CNR of Naples.

The main cause of fertility loss in Kallmann syndrome is impaired development and migration of neurons that produce gonadotropin-releasing hormone (GnRH), hormones produced by the adenohypophysis that regulate the reproductive functions of male and female sex organs. .

The first identified gene responsible for Kallmann syndrome (ANOS1) – He tells us Robert Maggieformer Professor of Physiology at the Institute of Pharmacological and Biomolecular Sciences and head of the Laboratory of Developmental Neuroendocrinology at the State University –encodes the anosmin-1 protein, which has been found to be involved in the development of GnRH neurons and olfactory connections. The absence of this gene in mainly rodents used as a test model has so far prevented detailed investigation of the role of anosmin-1, and many studies have focused on the possible replacement of anosmin-1 in such animals“.

In the published study, the research team was therefore able to show that olfactorin, the product of the UMODL1 (uromodulin-like 1) gene, which is expressed in the mouse olfactory region along the migratory pathway of GnRH neurons, has a strong structural and functional commonality Similarity to Anosmin-1.

We were able to show that olfactorin behaves very similarly to anosmin-1 by stimulating the migration of GnRH neurons in vitro and the development of the GnRH and olfactory systems in zebrafish animal models. – continues Professor Maggi. It is interesting to note that in humans, the UMODL1 gene is present on chromosome 21, which is known to be involved in the etiopathogenesis of Down’s syndrome, and about 40% of patients affected by this syndrome have reproductive and olfactory disorders that have not yet been explained. I study – concludes Roberto Maggi – therefore proposes olfactorin as another factor involved in the development of the olfactory system, and GnRH possibly involved in the onset of both Kallmann and Down syndrome“.