Mouse models for inherited monoamine neurotransmitter disorders.
J Inherit Metab Dis
; 47(3): 533-550, 2024 05.
Article
in En
| MEDLINE
| ID: mdl-38168036
ABSTRACT
Several mouse models have been developed to study human defects of primary and secondary inherited monoamine neurotransmitter disorders (iMND). As the field continues to expand, current defects in corresponding mouse models include enzymes and a molecular co-chaperone involved in monoamine synthesis and metabolism (PAH, TH, PITX3, AADC, DBH, MAOA, DNAJC6), tetrahydrobiopterin (BH4) cofactor synthesis and recycling (adGTPCH1/DRD, arGTPCH1, PTPS, SR, DHPR), and vitamin B6 cofactor deficiency (ALDH7A1), as well as defective monoamine neurotransmitter packaging (VMAT1, VMAT2) and reuptake (DAT). No mouse models are available for human DNAJC12 co-chaperone and PNPO-B6 deficiencies, disorders associated with recessive variants that result in decreased stability and function of the aromatic amino acid hydroxylases and decreased neurotransmitter synthesis, respectively. More than one mutant mouse is available for some of these defects, which is invaluable as different variant-specific (knock-in) models may provide more insights into underlying mechanisms of disorders, while complete gene inactivation (knock-out) models often have limitations in terms of recapitulating complex human diseases. While these mouse models have common phenotypic traits also observed in patients, reflecting the defective homeostasis of the monoamine neurotransmitter pathways, they also present with disease-specific manifestations with toxic accumulation or deficiency of specific metabolites related to the specific gene affected. This review provides an overview of the currently available models and may give directions toward selecting existing models or generating new ones to investigate novel pathogenic mechanisms and precision therapies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neurotransmitter Agents
/
Disease Models, Animal
Limits:
Animals
/
Humans
Language:
En
Journal:
J Inherit Metab Dis
Year:
2024
Document type:
Article
Affiliation country:
Suiza