Why Pigs?

The Pig as an Animal Model

For decades, the pig has been utilized as a preclinical animal model across a multitude of fields, but

why has it gained so much popularity?

It is due to the many shared features with humans:

Related pig and human features including neurotransmitter concentrations, gyrencephalic brain, intestinal anatomy, microbiota diversity, and nutrient requirements. — **Figure 1.** Pigs share multiple features with humans making them a useful biomedical animal model in research. First, pigs have a *gyrencephalic brain* meaning they have a similar folded cerebral cortex like humans and have larger cortical surface area. Along with similar neuroanatomy, many *neurotransmitter concentrations* are in similar areas, such as serotonin primarily in the thalamus, raphe nucleus, and basal ganglia. They also have shared *intestinal anatomy*, comparable digestive transit times, similar *nutrient requirements* – especially during development, and they are both colon fermenters leading to similar *communities of microbiota* within the gut.

Which makes them an excellent model for studying the microbiota-gut-brain axis.

The Current Challenge

A significant obstacle is how do we translate what we find in the pig to the human?
The differences in timing of development make translation a difficult task.

Pig and infant showcasing currently there is no way to transfer information from the pig to the human.

This was true for many other species, which led Clancy and colleagues in 2001 to create the Translating Time model which estimates the timing of 95 neurodevelopmental events across 9 species.

Read the original article.

With this model, one can estimate when a neurodevelopmental event, such as peak of neurogenesis of the cranial motor nuclei, in a species like the hamster occurs and directly compare it to when it occurs in the human. Each species is assigned a species score and each event an event score.

An excerpt of the table from the Clancy et al. (2001) paper where they established the translating mammalian time regression model. — **Table 1.** This is an excerpt of Table 1 from Clancy et al., (2001), representing the predicted post-conception days that each selected neural event occurs across their selected nine mammalian species. In this table each column (outlined in the blue square) represents the species of interest, with the corresponding **species score** that was determined with their model. The closer the value is to 0.663, the closer a species is to the neurodevelopmental rate of a hamster. The closer the species score is to 2.5, the closer the species is to the neurodevelopmental rate of a human. Each row (outlined in the red square) represents a selected **neural event** (in total there are 95) **with a unique score**. Each of these events correspond to neurogenesis – when it starts, peaks, or ends - in a given neural area. Using both the **species score** and **event score**, one can use their regression model to predict on what post-conception day an event will occur.

A notable animal, the pig, is missing from this model which invite the questions:
Where does the pig belong?
How close in neurodevelopmental proximity is it to the human?

Pig in a dashed circle with a question mark

Establishing the Pig as a Neurodevelopmental Model

Our Objective

To conduct a comprehensive literature review to identify as many of the 95 neurodevelopmental events in the pig as possible to enable a chronological comparison.

Read the full article

The Results

30 neurodevelopmental events identified.
Two optimization procedures utilized.
The pig species score was determined to be 2.157 placing it right between the cat and macaque.

Representing where the pig belongs amongst other mammals in terms of neurodevelopment from shortest to longest as hamster (0.663), mouse (0.701), rat (0.897), rabbit (1.098), ferret (1.714), cat (1.808), pig (2.157), macaque monkey (2.255), and human (2.500). — **Figure 2.** Pig species placement in the translating time model. This figure depicts the positioning of the domestic pig in the translating time model created by Clancy et al. (2001). The pig was determined to have a species score of 2.157, placing it right between the cat (1.808) and the macaque (2.255). At the lowest end of the model sits the hamster (0.663), followed by the mouse (0.701), rat (0.897), rabbit (1.098), spiny mouse (1.177, not pictured), and the ferret (1.714). At the highest end after the macaque (2.255) is the human infant with a species score of 2.500.

Interactive Translating Time Graphic

As a result of our comprehensive literature we have created this interactive graph that establishes a chronological neurodevelopmental timeline across four species: the mouse, pig, macaque, and human.

All 95 neurodevelopmental events with corresponding event scores from 0.903 (Cranial Motor Nuclei - peak) to 2.546 (Eye Opening) from the Clancy et al., (2001) manuscript are included.
To find a specific event and on which post-conception day it is estimated the event occurs, use the drop-down menu. The first event starts with the cranial motor nuclei - peak (corresponding post-conception days (PCD): Mouse = 9.39, Pig = 25.68, Macaque = 27.87, Human = 34.38) and the last event is eye-opening (corresponding PCDs: Mouse = 30.24, Pig = 115.14, Macaque = 126.54, Human = 160.44).
Using these 95 neurodevelopmental events, we estimated the resulting chronological timeline across all 4 species. Many of these post-conception days do not have corresponding events associated with them and are a rough estimate of where these different species are in terms of developmental time.
In the original Clancy et al., (2001) model, PCDs for the macaque and human were adjusted if the event in question was part of the limbic (- 0.09031) or cortical (+ 0.21722) system. These adjusted PCDs can be found under the relevant events (if no adjusted PCD is listed, the event in question was not adjusted) in the text to the left. Read the original article to learn more.

Pig Imaging Group

Beckman Institute for Advanced Science and Technology