Development and characterization of an inducible mouse model for glycogen storage disease type Ib

Raggi, Federica; Pissavino, Anna Livia; Resaz, Roberta; Segalerba, Daniela; Puglisi, Andrea; Vanni, Cristina; Antonini, Francesca; Zotto, Genny Del; Gamberucci, Alessandra; Marcolongo, Paola; Bosco, Maria Carla; Grillo, Federica; Mastracci, Luca; Eva, Alessandra

doi:10.1007/s10545-018-0211-2

Cited by 6 publications

(17 citation statements)

References 25 publications

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“…6–8-week-old G6PT lox/lox .creER/wt mice, hereafter referred to as G6PT +/+ , were injected intraperitoneally with 1 mg/10 g body weight/day of tamoxifen (TM) for five consecutive days to obtain TM-G6PT −/− mice, as described (9) . Dapagliflozin was obtained from AstraZeneca (NCR-16-12,171) and administered to adult mice in drinking water (1.5 mg/kg/day) for 10 days, starting three days before TM induction.…”

Section: Methodsmentioning

confidence: 99%

“…Bone marrow (BM) cells were harvested from femoral and tibia bones by flushing with 3 ml of PBS. Neutrophils were harvested as previously described (9) . Analysis of neutrophil functional activity and hematopoietic progenitor cell assays were performed with standard techniques, as described (9) .…”

Section: Methodsmentioning

confidence: 99%

“…We have addressed the problem of neutrophil dysfunction in a mouse model of GSDIb (9) . We report here that dapagliflozin treatment significantly improves myeloid cells' function in these mice.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The SGLT2-inhibitor dapagliflozin improves neutropenia and neutrophil dysfunction in a mouse model of the inherited metabolic disorder GSDIb

Resaz

Raggi

Segalerba

et al. 2021

Molecular Genetics and Metabolism Reports

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The SGLT2-inhibitor dapagliflozin improves neutropenia and neutrophil dysfunction in a mouse model of the inherited metabolic disorder GSDIb

Resaz

Raggi

Segalerba

et al. 2021

Molecular Genetics and Metabolism Reports

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“…TM treatment was administered in mice at 6-8 weeks for 5 consecutive days. Except for the lack of growth retardation, the phenotype was similar to that of patients (i.e., hepatomegaly and nephromegaly with glycogen accumulations in these two tissues, increased serum cholesterol and triglyceride levels, as well as neutropenia and neutrophil dysfunction and mild even monocyte dysfunction) [135].…”

Section: Mouse Models For Gsd-ibmentioning

confidence: 61%

“…The TM-Slc37a4 -/mouse model is a conditional G6P T -deficient model that allows a temporal regulation of Slc37a4 gene deletion with the administration of TM, avoiding the premature death of mice and leading to a long-term physiopathology model [135]. TM-Slc37a4 -/mice were generated using an inducible Cre-lox strategy, which resulted in the specific excision of exons 2, 3, 4 and 5 in both Slc37a4 alleles when TM was administered.…”

Section: Mouse Models For Gsd-ibmentioning

confidence: 99%

Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models

Almodóvar-Payá

Villarreal-Salazar

Luna

et al. 2020

IJMS

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GSD are a group of disorders characterized by a defect in gene expression of specific enzymes involved in glycogen breakdown or synthesis, commonly resulting in the accumulation of glycogen in various tissues (primarily the liver and skeletal muscle). Several different GSD animal models have been found to naturally present spontaneous mutations and others have been developed and characterized in order to further understand the physiopathology of these diseases and as a useful tool to evaluate potential therapeutic strategies. In the present work we have reviewed a total of 42 different animal models of GSD, including 26 genetically modified mouse models, 15 naturally occurring models (encompassing quails, cats, dogs, sheep, cattle and horses), and one genetically modified zebrafish model. To our knowledge, this is the most complete list of GSD animal models ever reviewed. Importantly, when all these animal models are analyzed together, we can observe some common traits, as well as model specific differences, that would be overlooked if each model was only studied in the context of a given GSD.

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Gene therapy for glycogen storage diseases

Koeberl

Koch

Lim

et al. 2023

J of Inher Metab Disea

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Glycogen storage disorders (GSDs) are inherited disorders of metabolism resulting from the deficiency of individual enzymes involved in the synthesis, transport, and degradation of glycogen. This literature review summarizes the development of gene therapy for the GSDs. The abnormal accumulation of glycogen and deficiency of glucose production in GSDs lead to unique symptoms based upon the enzyme step and tissues involved, such as liver and kidney involvement associated with severe hypoglycemia during fasting and the risk of long‐term complications including hepatic adenoma/carcinoma and end stage kidney disease in GSD Ia from glucose‐6‐phosphatase deficiency, and cardiac/skeletal/smooth muscle involvement associated with myopathy +/− cardiomyopathy and the risk for cardiorespiratory failure in Pompe disease. These symptoms are present to a variable degree in animal models for the GSDs, which have been utilized to evaluate new therapies including gene therapy and genome editing. Gene therapy for Pompe disease and GSD Ia has progressed to Phase I and Phase III clinical trials, respectively, and are evaluating the safety and bioactivity of adeno‐associated virus vectors. Clinical research to understand the natural history and progression of the GSDs provides invaluable outcome measures that serve as endpoints to evaluate benefits in clinical trials. While promising, gene therapy and genome editing face challenges with regard to clinical implementation, including immune responses and toxicities that have been revealed during clinical trials of gene therapy that are underway. Gene therapy for the glycogen storage diseases is under development, addressing an unmet need for specific, stable therapy for these conditions.

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Development and characterization of an inducible mouse model for glycogen storage disease type Ib

Abstract: TM-induced inactivation of G6PT in these mice leads to a phenotype which mimics that of human GSD1b patients. The conditional mice we have generated represent an excellent tool to study the tissue-specific role of the G6PT gene and the mechanism of long-term complications in GSD1b.

Cited by 6 publications

References 25 publications

The SGLT2-inhibitor dapagliflozin improves neutropenia and neutrophil dysfunction in a mouse model of the inherited metabolic disorder GSDIb

The SGLT2-inhibitor dapagliflozin improves neutropenia and neutrophil dysfunction in a mouse model of the inherited metabolic disorder GSDIb

Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models

Gene therapy for glycogen storage diseases

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