Mouse Organ-Specific Proteins and Functions

Abstract

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them—such as alanine transaminase, aspartate transaminase, and troponins—in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

Capture of the Mouse Organ Membrane Proteome Specificity in Peptidisc Libraries

“…More than just membrane protein identification, our results show that the peptidisc can be used as a proxy to estimate the relative abundance of pIMPs across organs, allowing us to link protein molecular functions and abundances to organ biological roles. As reported by others, the biological functions of organs and constitutive tissues are mainly guided by quantitative rather than qualitative proteome differences. ,, We present here compelling evidence that the relative abundance of the pIMPs in peptidisc is reflecting the essence of the organ’s biological functions (Figure ). For instance, processes like “synaptic signaling” are found to be uniquely associated with the brain data set, whereas the presence of abundant “sodium ion cotransporters” in the kidney aligns with the organ’s function in reabsorbing nutrients .…”

“…The precise knowledge of these organ-specific proteins, whose expression is significantly elevated in a given organ, holds great medical significance. For instance, several clinical diagnostics rely upon organ-specific protein biomarkers to monitor pathological states and disease progression, whereas the development of therapeutics critically depends on understanding organ specificity to prevent cross-reactivity. , This knowledge is especially important at the cell surface since about two-thirds of the druggable proteome comprises integral membrane proteins. , Perturbation of the membrane proteome is also linked to neurodegenerative diseases, cancer, and disorders like hypertension and muscular dystrophy. − Genomic and transcriptomic technologies have undeniably proven their worth by shedding light on organ protein expression patterns. − Still, to achieve a comprehensive understanding of organ biology at a molecular level, a direct estimate of its protein content is imperative. − …”

Single Isotopologue for In-Sample Calibration and Absolute Quantitation by LC-MS/MS

“…The heart is a complex and vital organ, and its proteome has been subjected to intense global proteomics characterization. − The efficiency of enzymatic digestion and sample recovery of heart membrane proteomes has never been quantitatively studied. In the past, we analyzed the proteomes of 13 major mouse organs in four inbred strains to investigate the dynamics of organ-specific proteins, including the heart. We used the modified sample preparation protocol from our previous work and used porcine heart as a model to examine the efficiency of digestion and sample recovery under three conditions using two types of commercial trypsin with varied digestion durations.…”

“…Dissected heart tissue was stored at −80 °C for further processing. Protein extraction from porcine ventricles followed our previously published protocol 19 with minor modifications. In detail, a ceramic mortar was chilled with liquid nitrogen, and the frozen heart tissue was shattered in liquid nitrogen held by the mortar and collected in Eppendorf vials.…”

Neurotoxicity of Silver Nanoparticles and Non-Linear Development of Adaptive Homeostasis with Age

“…After conducting a battery of behavioral tests, the animals (n = 6–8 in each subgroup) were anesthetized with isoflurane (Baxter, Aibonito, Puerto Rico, USA) and decapitated; the organs (liver, spleen, lungs, kidneys, brain, heart, testes) and their blood were collected. This protocol was based on the widely used procedures [ 32 , 33 ]. Tissue samples were dried in a RedLine RF 53 drying chamber (Binder GmbH, Tuttlingen, Germany) for 72 h at 75 °C for further irradiation in the channel of a nuclear reactor.…”