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Animal Model Contributions to Congenital Metabolic Disease

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Animal Models of Human Birth Defects

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1236))

Abstract

Genetic model systems allow researchers to probe and decipher aspects of human disease, and animal models of disease are frequently specifically engineered and have been identified serendipitously as well. Animal models are useful for probing the etiology and pathophysiology of disease and are critical for effective discovery and development of novel therapeutics for rare diseases. Here we review the impact of animal model organism research in three examples of congenital metabolic disorders to highlight distinct advantages of model system research. First, we discuss phenylketonuria research where a wide variety of research fields and models came together to make impressive progress and where a nearly ideal mouse model has been central to therapeutic advancements. Second, we review advancements in Lesch-Nyhan syndrome research to illustrate the role of models that do not perfectly recapitulate human disease as well as the need for multiple models of the same disease to fully investigate human disease aspects. Finally, we highlight research on the GM2 gangliosidoses Tay-Sachs and Sandhoff disease to illustrate the important role of both engineered traditional laboratory animal models and serendipitously identified atypical models in congenital metabolic disorder research. We close with perspectives for the future for animal model research in congenital metabolic disorders.

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Abbreviations

BH4:

Tetrahydrobiopterin

CMD:

Congenital metabolic disorder

ENU:

Ethylnitrosurea

ES:

Embryonic stem cell

GM2:

G represents gangliosides, M indicates monosialic, and 2 indicates second monosialic ganglioside discovered

HEXA, HEXA:

Human acetylhexosaminidase α subunit protein and gene, respectively. HEXA also refers to the enzymatic activity of the hexosaminidase α/β dimer

Hexa, Hexa:

Mouse acetylhexosaminidase α subunit protein and gene, respectively

HEXB, HEXB:

Human acetylhexosaminidase β subunit protein and gene, respectively. HEXB also refers to the enzymatic activity of the hexosaminidase β dimers

Hexb, Hexb:

Mouse acetylhexosaminidase β subunit protein and gene, respectively

HEXS:

Refers to the enzymatic activity of the hexosaminidase α dimers

HPRT, HPRT:

Human hypoxanthine-guanine phosphoribosyltransferase protein and gene, respectively

Hprt, Hprt:

Rodent hypoxanthine-guanine phosphoribosyltransferase protein and gene, respectively

IEM:

Inborn error of metabolism

iPS:

Induced pluripotent stem cells

LNS:

Lesch-Nyhan syndrome

PAH, PAH:

Human phenylalanine hydroxylase protein and gene, respectively

Pah, Pah:

Rodent phenylalanine hydroxylase protein and gene, respectively

PAL:

Phenylalanine ammonia lyase

PEG:

Polyethylene glycol

PKU:

Phenylketonuria

SD:

Sandhoff disease

THBD:

Tetrahydrobiopterin deficiency

TSD:

Tay-Sachs disease

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    Corinna A. Moro & Wendy Hanna-Rose

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    Aimin Liu

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Moro, C.A., Hanna-Rose, W. (2020). Animal Model Contributions to Congenital Metabolic Disease. In: Liu, A. (eds) Animal Models of Human Birth Defects. Advances in Experimental Medicine and Biology, vol 1236. Springer, Singapore. https://doi.org/10.1007/978-981-15-2389-2_9

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