Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Journal of Inherited Metabolic Disease Année : 2015

Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease

Résumé

Patients with glycogen storage diseases type 1 (GSD1) suffer from life-threatening hypoglycaemia, when left untreated. Despite an intensive dietary treatment, patients develop severe complications, such as liver tumors and renal failure, with aging. Until now, the animal models available for studying the GSD1 did not survive after weaning. To gain further insights into the molecular mechanisms of the disease and to evaluate potential treatment strategies, we have recently developed novel mouse models in which the catalytic subunit of glucose-6 phosphatase (G6pc) is deleted in each glucose-producing organ specifically. For that, B6.G6pcex3lox/ex3lox mice were crossed with transgenic mice expressing a recombinase under the control of the serum albumin, the kidney androgen protein or the villin promoter, in order to obtain liver, kidney or intestine G6pc-/- mice, respectively. As opposed to total G6pc knockout mice, tissue-specific G6pc deficiency allows mice to maintain their blood glucose by inducing glucose production in the other gluconeogenic organs. Even though it is considered that glucose is produced mainly by the liver, liver G6pc-/- mice are perfectly viable and exhibit the same hepatic pathological features as GSD1 patients, including the late development of hepatocellular adenomas and carcinomas. Interestingly, renal G6pc-/- mice developed renal symptoms similar to the early human GSD1 nephropathy. This includes glycogen overload that leads to nephromegaly and morphological and functional alterations in the kidneys. Thus, our data suggest that renal G6Pase deficiency per se is sufficient to induce the renal pathology of GSD1. Therefore, these new mouse models should allow us to improve the strategies of treatment on both nutritional and pharmacological points of view.
Fichier principal
Vignette du fichier
Rajas et al.-JMID 2015.pdf (561.04 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

inserm-01350960 , version 1 (02-08-2016)

Identifiants

Citer

Fabienne Rajas, Julie Clar, Amandine Gautier-Stein, Gilles Mithieux. Lessons from new mouse models of glycogen storage disease type 1a in relation to the time course and organ specificity of the disease. Journal of Inherited Metabolic Disease, 2015, 38 (3), pp.521-527. ⟨10.1007/s10545-014-9761-0⟩. ⟨inserm-01350960⟩
133 Consultations
221 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More