Obesity Preclinical Contract Research Solutions

Online Inquiry

First Name *

Last Name *

Business Email *

Phone

Company/Institution

Job Title

Services of Interest *

When do you expect your project to start?

Project Description

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

MC4R Knockout Mouse Models for Monogenic Obesity Research

Inquiry

At Ace Therapeutics, we specialize in delivering tailored preclinical research solutions to accelerate drug discovery for metabolic disorders. Our expertise lies in leveraging cutting-edge genetic models, including the MC4R knockout mouse, to study monogenic obesity mechanisms and evaluate therapeutic candidates with precision. This page outlines how our services empower researchers to advance obesity-related interventions through robust preclinical data generation.

Understanding the MC4R Knockout Mouse Model

The melanocortin-4 receptor (MC4R) plays a central role in regulating energy homeostasis, appetite, and body weight. Mutations or deletions in the MC4R gene are strongly associated with early-onset severe obesity in humans, making this pathway a critical target for therapeutic intervention. The MC4R knockout mouse model recapitulates key features of monogenic obesity, including hyperphagia, reduced energy expenditure, and metabolic dysregulation, providing a physiologically relevant platform for preclinical studies.

Fig 1. Mc4r heterozygous mice. Fig.1. The efficacy and safety of autoregulatory BDNF gene therapy in Mc4r heterozygous mice. (Siu, J. J., et al. 2017)

Why Choose the MC4R Knockout Mouse Model
Human Disease Relevance	Genetically engineered MC4R-deficient mice exhibit obesity phenotypes closely aligned with human monogenic obesity, enabling translational insights into drug mechanisms.
Target Validation	This model allows researchers to investigate compounds targeting the melanocortin pathway, downstream signaling effectors, or compensatory metabolic networks.
Comprehensive Phenotypic Profiling	Using longitudinal body composition analysis (via DEXA), metabolic cage assessments (oxygen consumption, locomotor activity), and hormonal/cytokine profiling to capture multi-dimensional efficacy data.

MC4R Knockout Mouse Model-Based Preclinical Services

Ace Therapeutics stands at the forefront of preclinical research in the field of obesity. We specialize in leveraging the MC4R Knockout Mouse, a well-established monogenic obesity model, to deliver robust and scientifically sound preclinical studies.

Pharmacodynamic & Efficacy Testing

Evaluate candidate molecules for their ability to mitigate obesity-associated parameters

Body weight trajectory analysis
Food intake monitoring under controlled conditions
Glucose tolerance and insulin sensitivity assessments
Lipid metabolism profiling

Mechanism of Action (MoA) Studies

Uncover therapeutic effects at molecular and cellular levels

Hypothalamic signaling pathway analysis (qPCR, Western blot)
Receptor binding/activation assays for MC4R-targeted therapies
Neural circuit mapping to assess central vs. peripheral effects

Safety & Tolerability Assessments

Integrate obesity-specific endpoints with standard toxicology readouts

Cardiovascular function monitoring (telemetry-based)
Behavioral studies to detect CNS-related adverse effects
Organ-specific histopathology in metabolic tissues

Customizable Study Designs for Diverse Research Goals

Our team collaborates with clients to develop protocol-driven studies aligned with project objectives. Whether screening early-stage compounds or optimizing lead candidates, we adapt variables such as

Dosing regimens (acute vs. chronic administration)
Dietary conditions (chow, high-fat diet, or customized formulations)
Age-matched cohorts to model pediatric or adult obesity
Combination therapy testing with existing anti-obesity agents

Data Integrity & Translational Relevance

Ace Therapeutics employs rigorous experimental standards to ensure reproducibility and clinical relevance

Strict environmental controls (temperature, light cycles, housing density)
Age- and sex-matched littermate controls to minimize variability
Blinded data acquisition and statistical analysis
Comparative datasets from wild-type and heterozygous cohorts

Frequently Asked Questions (FAQ) About ob/ob Mouse Model

How does the MC4R knockout model differ from diet-induced obesity (DIO) models?

The MC4R knockout model replicates monogenic obesity driven by specific genetic disruption, offering a controlled system to study MC4R-linked pathways. In contrast, DIO models reflect polygenic/metabolic interactions. Combined studies using both models can elucidate compound efficacy across obesity subtypes.

Can you accommodate studies requiring tissue-specific MC4R restoration?

Yes. We collaborate with clients to design conditional knockout/rescue studies using Cre-lox or AAV-mediated approaches, enabling spatial-temporal investigation of MC4R function.

What endpoints are recommended for early-stage compound screening?

Core metrics include weekly body weight trends, cumulative food intake, and glucose tolerance. For mechanism-focused studies, we recommend hypothalamic gene expression profiling or cAMP signaling assays.

How do you control for genetic background variability?

All studies use age-matched littermate controls maintained on identical C57BL/6J backgrounds. Heterozygous and wild-type cohorts are bred in-house under standardized conditions.

Are longitudinal metabolic assessments feasible in this model?

Absolutely. Our metabolic cage systems support continuous monitoring of energy expenditure, respiratory quotient, and locomotor activity over 72-hour periods, with optional high-fat diet challenges.

Reference

Siu, J. J., et al. (2017). Molecular Therapy of Melanocortin-4-Receptor Obesity by an Autoregulatory BDNF Vector. Molecular therapy. Methods & clinical development. 7, 83–95.