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Animal Models

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Identifying Potential Dietary Treatments for Inherited Metabolic Disorders Using Drosophila Nutrigenomics

Martelli et al., Cell Reports. 2024.

https://www.sciencedirect.com/science/article/pii/S221112472400189X?via%3Dihub=

Inherited metabolic disorders are known to cause severe neurological impairment and child mortality and can sometimes respond to dietary treatment; however, a suitable paradigm for testing diets is lacking for developing effective dietary treatment. In this study, researchers found that 26 of 35 Drosophila amino acid disorder models screened for disease–diet interactions displayed diet-altered development and/or survival. Among these models, researchers showed that dietary cysteine depletion normalizes metabolic profile and rescues development, neurophysiology, behavior, and life span in a model for isolated sulfite oxidase deficiency. These findings demonstrate the value of using Drosophila in studying diet-sensitive metabolic disorders and developing potential dietary therapies. Supported by ORIP (R24OD031447) and NHGRI.

PGRN Deficiency Exacerbates, Whereas a Brain Penetrant PGRN Derivative Protects, GBA1 Mutation–Associated Pathologies and Diseases

Zhao et al., Proc Natl Acad Sci USA. 2023.

https://www.pnas.org/doi/10.1073/pnas.2210442120

Mutations in GBA1 are associated with Gaucher disease (GD) and are also genetic risks in developing Parkinson’s disease (PD). Investigators created a mouse model and demonstrated that progranulin (PGRN) deficiency in Gba1 mutant mice caused early onset and exacerbated GD phenotypes, leading to substantial increases in substrate accumulation and inflammation in visceral organs and the central nervous system. These in vivo and ex vivo data demonstrated that PGRN plays a crucial role in the initiation and progression. In addition, the mouse model provides a clinically relevant system for testing therapeutic approaches for GD and PD. Supported by ORIP (R21OD033660), NIAMS, and NINDS.

Multiplexed Drug-Based Selection and Counterselection Genetic Manipulations in Drosophila

Matinyan et al., Cell Reports. 2021.

https://www.cell.com/cell-reports/pdf/S2211-1247(21)01147-5.pdf

Many highly efficient methods exist which enable transgenic flies to contribute to diagnostics and therapeutics for human diseases. In this study, researchers describe a drug-based genetic platform with four selection and two counterselection markers, increasing transgenic efficiency by more than 10-fold compared to established methods in flies. Researchers also developed a plasmid library to adapt this technology to other model organisms. This highly efficient transgenic approach significantly increases the power of not only Drosophila melanogaster but many other model organisms for biomedical research. Supported by ORIP (P40OD018537, P40OD010949, R21OD022981), NCI, NHGRI, NIGMS, and NIMH.