The genome carries the blueprints for life, but the actual work inside cells is performed by proteins. The entire collection of proteins expressed by an organism, cell, or tissue is known as the proteome. Understanding cellular function requires knowing which proteins are present, where they are located, and how abundant they are. The Mouse Protein Atlas (MPA) is a powerful, publicly available resource designed to systematically map and catalog this collection of proteins in a mammalian system. This resource allows researchers to explore protein function and localization in mice, providing a crucial window into the molecular mechanisms that govern health and disease.
Defining the Mouse Protein Atlas
The Mouse Protein Atlas is an extensive, open-access database that systematically catalogs the expression and localization of most protein-coding genes in the mouse genome. It was launched as an expansion of the broader Human Protein Atlas (HPA) project, which aims to map all human proteins. By extending the methodology to the mouse, the MPA offers a direct and comparative view of the proteome in a model organism.
The data is generated using highly specific molecular techniques to ensure an accurate profile of protein expression. One primary method is immunohistochemistry (IHC), which uses antibodies to visually detect and localize specific proteins within tissue sections. This process provides high-resolution spatial information, showing exactly which cells and structures are producing a given protein.
Another technique employed is RNA sequencing (RNA-seq), which measures the amount of messenger RNA (mRNA) transcripts present in a sample. Since mRNA is the template for protein production, measuring its levels offers an estimate of protein abundance across various tissues and cell types. Researchers also utilize mass spectrometry-based proteomics, which identifies and quantifies thousands of individual proteins across different tissues. The integration of these diverse datasets creates a detailed, multi-dimensional map of the mouse proteome.
Mapping Protein Expression Across Mouse Tissues
A core function of the Mouse Protein Atlas is to visualize and organize protein expression data across the entire animal, providing a body-wide map. This detailed mapping includes tissue specificity, cell type specificity, and subcellular localization. Researchers can determine if a protein is expressed globally across all tissues, like a housekeeping protein, or if it is highly specific to a single organ.
The atlas provides visual evidence for protein location, allowing scientists to pinpoint where the protein resides within the cellular architecture. Subcellular mapping shows whether a protein is localized to the nucleus, mitochondria, the Golgi apparatus, or the cell membrane. This location is a powerful indicator of the protein’s probable function; for example, a protein found exclusively in the nucleus is likely involved in gene regulation.
Specific components, such as the data from the Allen Mouse Brain Atlas, provide a granular view of protein expression within complex organs. This sub-atlas uses techniques like in situ hybridization to map gene expression across hundreds of distinct anatomical regions of the mouse brain. This spatial resolution is instrumental for inferring a protein’s role in neural circuitry, development, and neurological function. By cataloging expression patterns in such detail, the MPA provides a functional context for every protein.
Why Mouse Models are Essential for Proteomics
The mouse is the most widely used mammalian model in biomedical research due to its genetic similarity to humans. Mice and humans share approximately 70% of the same protein-coding gene sequences, meaning many molecular mechanisms are highly conserved between the two species. Furthermore, the organization of genes on chromosomes, known as synteny, is preserved across large segments.
The mouse model offers a highly controlled experimental system that is not feasible in human studies. Researchers can breed genetically uniform strains, minimizing genetic variability that could confound experimental results. This control is paramount for proteomics studies, where subtle changes in protein expression need to be isolated and accurately measured.
Another advantage is the ability to easily manipulate the mouse genome to create specific disease models. Researchers can create “knockout” mice, where a specific gene is deleted or silenced, to study the resulting effects on the proteome and the organism’s physiology. These models allow for the investigation of proteins involved in complex diseases like cancer, diabetes, and neurodegeneration. While differences exist, the mouse remains an unparalleled tool for understanding general mammalian biology.
Translational Insights into Human Disease
The data contained within the Mouse Protein Atlas serves as a critical bridge for translating discoveries into human health applications. Researchers routinely perform cross-species analysis, comparing mouse protein expression patterns to the corresponding data in the Human Protein Atlas. This comparison helps validate whether a finding in a mouse model is likely to be relevant in human biology, or it can highlight species-specific differences.
This comparative approach is useful in identifying and validating novel therapeutic targets for drug discovery. For example, if a protein is highly expressed in a specific tumor type in a mouse cancer model, its expression pattern can be cross-referenced with human tumor data. The MPA provides a crucial “roadmap” that guides preclinical research, allowing scientists to predict the potential side effects of a drug by checking if the protein target is also expressed in unintended healthy tissues.
The MPA also accelerates the understanding of disease mechanisms by providing context for proteins implicated in genetic disorders. When a human genetic study identifies a gene mutation associated with a disease, the MPA can quickly provide information on where the corresponding mouse protein is located and what other proteins it might interact with. This molecular detail helps researchers hypothesize and test the protein’s role in the disease pathology. By providing a comprehensive, accessible resource for mammalian protein function, the Mouse Protein Atlas directly supports the development of new diagnostic biomarkers and more effective treatments for human diseases.