Burrowing Behavior in Mice

Genetics 198 Review Paper: Genetics and Implications of Burrowing

Behavior in Mice
Yashika Patil
University of Rochester

Burrowing Behavior in Mice

2
Abstract

Burrowing in mice was observed by various researchers. While some observed

how it evolved, others observed how it could be used to develop treatments for
humans. Hoekstra and Weber (2009) observed that in seven species of mice,
only P. polionotus build complex burrows and concluded that this behavior is a
result of small genetic changes over time. They later found that complex
burrowing behavior segregates in a dominant fashion (2013). While three
alleles are responsible for the entrance-length of the tunnel, only one is
responsible for the exit tunnel. Other researchers found a correlation between
injuries like, inflammation in knee joints and peripheral nerve injuries, and the
burrowing in mice. They then tested the effectiveness of various drugs that
restored the deficit. While still others, found a correlation between brain
lesions and burrowing, which could be linked with Alzheimer's in humans and
further tested to develop a treatment using this link.

Burrowing Behavior in Mice

3
Introduction

Mice have been extensively used in experiments because of their small size,
adaptability to new surroundings, short life cycle, and the ease to procure
them. Their behaviors can be observed to draw larger biological conclusions.
One such behavior of great biological significance is the burrowing in mice.
Different species of mice burrow differently, but the act itself can be used to
observe the effects of stimuli, for example an injury, and the effectiveness of
analgesics. Although burrowing behavior has been studied for a while now, it
is only recently that studies on the genetic for the behavior have been
performed. The main questions this paper will answer is how the genetic
evolution of behavior led to the complex burrowing in Peromyscus polionotus,
what genetic factors are responsible for it, and what implications experiments
on burrowing have for humans.
Current Status of Knowledge
Evolution of Burrowing Behavior
Hopi Hoekstra is a zoology professor at Harvard University. Her lab studies
the molecular, genetic, and developmental basis of evolutionary change in
rodents. It is she and her postdoc student Jesse Weber (2009) that put together
the evolutionary history of burrowing behavior. They experimented on seven
species of deer mice and observed the burrows' entrance lengths, depths, total
lengths, entrance angles, frequencies of burrowing. In the wild, they had
observed that different species build different shapes and sizes of burrows.
While P. polionotus build complex burrows with a long entrance tunnel,
resting nest, and a long exit tunnel that stopped just below the surface of the
soil, others like P. maniculatus, and P. melanophrys built simple burrows,
while still others like P. californicus and P. eremicus did not build any burrow.
Hoekstra and Weber built a phylogeny for this trait and observed if the
evolution was a result of environmental or genetic changes. Several
generations after being captive bred in the laboratory, the mice repeated their
behavior, suggesting that it is an innate behavior, as a result of genetic
variation between the species. The phylogeny (Figure 1) was created by
analyzing four mtDNA and two autosomal loci (Hoekstra and Weber, 2009,
figure 2).

Burrowing Behavior in Mice

Figure 1

This shows that the complex burrowing behavior has evolved, mostly due to
small genetic changes. The burrowing performance was not affected by age,
gender and temperature, except in P. maniculatus where entrance angle was
positively correlated with individual's age, males burrowed more than females,
and burrow shape was negatively correlated with temperature. P. polionotus
and P. aztecus build the longest burrows but only P. polionotus built complex
burrows. In discussion, Hoekstra and Weber (2009) conclude that based on
the phylogenetic pattern with large and complex burrows being derived, we
suggest the following evolutionary sequence: there was a propensity to dig,
existing tunnels were elongated, additional tunnels were added and then the
orientation of tunnels was fixed (e.g. angles of entrance and escape tunnels).
This progression suggests that complex burrowing probably evolved through
the gradual accumulation of genetic changes, some of which were probably
driven by natural selection (p. 608).

Burrowing Behavior in Mice

Genetic Modules Responsible for Complex Burrow Evolution
Hoekstra and Weber, along with Peterson (2013), found out the genes
responsible for the complex burrowing behavior in mice. They investigated P.
polionotus and P. maniculatus. As found in their previous experiment, P.
polionotus built complex burrows while P. maniculatus built simple burrows.
Under the laboratory conditions, both species still recapitulated their natural
burrowing behavior. Each assay involved placing a mouse in a large, sandfilled enclosure for 46 h (two full-night activity periods). Then, we removed
the mouse and made a polyurethane cast of the burrow which we them
measured (p. 403). The two mice species
were interbred the F1 individuals all
built significantly longer entrance tunnels
than P. maniculatus, but similar to P.
polionotus, and build escape tunnels.
Thus, the allele contributing to burrow
size and shape segregate in a dominant
fashion. A backcross of F1 individuals
with P. maniculatus was performed
[F2] mice constructed entrance tunnels
that varied continuously in length between
the parental extremes, but approximately
one of eight of the [F2] mice built P.
polionotus-length tunnels, suggesting that
only a few loci are necessary to generate
this behavior. In contrast, half of the [F2]
mice built escape tunnels. This inheritance
pattern is consistent with the action of
either a single major-effect locus or of
multiple loci that interact to create a
threshold effect, such that only some loci
need to be co-inherited to cause the
expression of a trait. Finally, tunnel
lengths and the presence of escape tunnels
(that is, tunnel number) are only weakly
correlated in [F2] mice Therefore, the
complex burrows of P. polionotus
comprise at least two separate behavioral
modules, one for tunnel length and one for
the presence of an escape tunnel (p. 403). Figure 2 (Hoekstra, Peterson and
Weber, 2013, figure 2) shows the burrow variation across generations.
They performed quantitative trait locus (QTL) mapping and identified three

Burrowing Behavior in Mice

genomic regions that contributed to variation in entrance-length, and a single

region associated with escape-tunnel construction. All four QTLs were
unlinked and segregated on separate chromosomes.
Implications for Humans
Burrowing behavior can be affected by injury in mice. Analgesics should
reinstate normal spontaneous daily behaviors. The effectiveness of analgesics
could be observed by observing the burrowing behavior in mice. The
experiments from the two papers, Andrews et al (2012) and Rutten et al (2013)
show that an injury decreases the burrowing behavior in mice. Ruten et al
(2013) observed weight-bearing, open-field activity, and burrowing in rats
after complete freund's adjuvant (CFA)-induced arthritis. Naproxen, ibuprofen,
and pregabalin reversed the CFA-induced deficits in burrowing. Andrews et al
(2012) observed that gabapentin at 30 mg/kg sc (but not 100 mg/kg sc)
reversed the deficit in burrowing induced by tibial nerve transection and
ibuprofen reversed the effect of CFA on burrowing. These experiments can be
used to determine the most effective drug for the specific injuries in humans.
On the other hand, Deacon (2012), related the burrowing behavior in mice to
Alzheimer's and other neurodegenerative diseases in humans. He observed that
mice with lesions in brain burrow less. Burrowing can detect prion (scrapie)
disease at 10-12 weeks after injection of diseased brain homogenate, whereas
clinical signs appear only after 22 weeks. This shows that burrowing is
directly related to brain injuries and can be further used to test effectiveness of
treatments, that can be later used for humans.
Conclusion
Complex burrowing has evolved due to small genetic changes because they
increase the mice's chances of survival from predators like snakes and birds.
The complex burrows are a result of four genes three responsible for
entrance-length of the tunnel and one responsible for the exit tunnel.
Mice burrowing can also be used to test the effectiveness of analgesics on
injuries, and further tests can be performed for understanding Alzheimer's
disease in humans. Although vastly useful, burrowing behavior in mice cannot
be solely depended on for these treatments, since it is an extended phenotype
that can be affected for reasons that have not yet been studied. Nevertheless,
burrowing in mice provides a priceless insight into the complexity of
evolution and the intricate genetics behind it. It is also very cheap and easy to
observe (Deacon 2012), which makes it a convenient testing criteria in many
experiments.

Burrowing Behavior in Mice

7
References

1. Andrews, N., Legg, E., Lisak, D., Issop, Y., Richardson, D., Harper, S.,
Pheby, T., Huang, W., Burgess, G., Machin, I. and Rice, A.S.C. (2012),
Spontaneous burrowing behaviour in the rat is reduced by peripheral
nerve injury or inflammation associated pain. European Journal of
Pain, 16: 485495. Retrieved June 3, 2015, from
http://onlinelibrary.wiley.com/doi/10.1016/j.ejpain.2011.07.012/abstrac
t;jsessionid=10A1E36F79715985B6117E07AD03E963.f02t03
2. Deacon, R. (2012). Assessing Burrowing, Nest Construction, and
Hoarding in Mice. Journal of Visualized Experiments: JoVE , (59),
2607. Retrieved June 12, 2015 from
http://www.jove.com/video/2607/assessing-burrowing-nestconstruction-and-hoarding-in-mice
3. Rutten, K., Schiene, K., Robens, A., Leipelt, A., Pasqualon, T., Read,
S., & Christoph, T. (2013, May 31). Burrowing as a non-reflex
behavioral readout for analgesic action in a rat model of sub-chronic
knee joint inflammation. European Journal of Pain, 18: 204-212.
Retrieved June 3, 2015, from
http://onlinelibrary.wiley.com.ezp.lib.rochester.edu/doi/10.1002/j.15322149.2013.00358.x/epdf
4. Weber, J., & Hoekstra, H. (2009, March 1). The evolution of
burrowing behavior in deer mice (genus Peromyscus). Animal
Behavior, 77: 603-609. Retrieved June 3, 2015, from
http://www.sciencedirect.com.ezp.lib.rochester.edu/science/article/pii/S
0003347208005460
5. Weber, J., Hoekstra, H., & Peterson, B. (2013, January 17). Discrete
genetic modules are responsible for complex burrow evolution in
Peromyscus mice. Nature, 493, 402-405. Retrieved June 3, 2015, from
http://www.nature.com/nature/journal/v493/n7432/full/nature11816.ht
ml