Neuroanatomical characterization of the Nmu-Cre knock-in mice reveals an interconnected network of unique neuropeptidergic cells

Author:

Medrano Mireia1,Allaoui Wissal1,Van Bulck Mathias2,Thys Sofie3,Makrini-Maleville Leila4,Seuntjens Eve5,De Vos Winnok H.367,Valjent Emmanuel4,Gaszner Bálazs8,Van Eeckhaut Ann1ORCID,Smolders Ilse1,De Bundel Dimitri1ORCID

Affiliation:

1. Center for Neurosciences, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, 1090 Brussels, Belgium

2. Laboratory of Medical and Molecular Oncology, Vrije Universiteit Brussel, 1090 Brussels, Belgium

3. Department of Veterinary Sciences, Laboratory of Cell Biology and Histology and Antwerp Centre for Advanced Microscopy (ACAM), University of Antwerp, 2610 Antwerp, Belgium

4. IGF, Université de Montpellier, CNRS, Inserm, 34094 Montpellier, France

5. Department of Biology, Laboratory of Developmental Neurobiology, KU Leuven, 3000 Leuven, Belgium

6. μNEURO Research Centre of Excellence, University of Antwerp, 2610 Antwerp, Belgium

7. Antwerp Centre for Advanced Microscopy (ACAM), 2610 Wilrijk, Belgium

8. Medical School, Research Group for Mood Disorders, Department of Anatomy and Centre for Neuroscience, University of Pécs, 7624 Pécs, Hungary

Abstract

Neuromedin U (NMU) is an evolutionary conserved neuropeptide that has been implicated in multiple processes, such as circadian regulation, energy homeostasis, reward processing and stress coping. Although the central expression of NMU has been addressed previously, the lack of specific and sensitive tools has prevented a comprehensive characterization of NMU-expressing neurons in the brain. We have generated a knock-in mouse model constitutively expressing Cre recombinase under the Nmu promoter. We have validated the model using a multi-level approach based on quantitative reverse-transcription polymerase chain reactions, in situ hybridization, a reporter mouse line and an adenoviral vector driving Cre-dependent expression of a fluorescent protein. Using the Nmu-Cre mouse, we performed a complete characterization of NMU expression in adult mouse brain, unveiling a potential midline NMU modulatory circuit with the ventromedial hypothalamic nucleus (VMH) as a key node. Moreover, immunohistochemical analysis suggested that NMU neurons in the VMH mainly constitute a unique population of hypothalamic cells. Taken together, our results suggest that Cre expression in the Nmu-Cre mouse model largely reflects NMU expression in the adult mouse brain, without altering endogenous NMU expression. Thus, the Nmu-Cre mouse model is a powerful and sensitive tool to explore the role of NMU neurons in mice.

Funder

Fondation Médicale Reine Elisabeth

FWO

Agence Nationale de la Recherche

Inserm, Fondation pour la Recherche Médicale

National Research, Development and Innovation Fund of Hungary

Fonds Wetenschappelijk Onderzoek

Fund for Scientific Research Flanders

Publisher

The Royal Society

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience

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