I'm wondering if anyone has ever noticed changing phenotypes in (transgenic) mice during the course of a year?
In detail, we observe that an embryonic lethality phenotype of one of our mouse strains seems to appear and vanish with the year's seasons. Does anybody have any idea how this can happen in a strictly controlled and stable, sterile environment like a mouse house, where the mice live under absolutely constant conditions?
Seasons seems indeed to affect mice, even in controlled conditions where they cannot "see" the seasons. It is generally accepted that breeding efficiency fluctuate over the seasons (usually fall being the worse period).
We did have issues with viability periodically and suspected that they may be seasonal but weren't sure. We wondered similarly, but your mouse room is not free from pollen, the water may be different, and there are other external factors, so it could be many things.
I've never heard of a change in transgenic phenotype related to seasons, but a few different labs that I have been with have noticed seasonal variability in breeding (mainly size of litters) even though the mice live in such a controlled environment. You might think of other things that could be changing during the year as well. We've noticed changes in breeding performance related to change in caregivers as well.
The environment is not nearly so stable as you think: first, it is sterile only for the diseases they check for, not numerous other diseases and viruses. Second, there will be seasonal changes that come in with the bedding - if you use corn husk bedding, there will be a different complement of fungi etc. on the bedding. There may also be seasonal changes with the food. I have seen definite seasonal changes in inflammatory state (in detail) in my mice - although it's subtle enough it's hard to see how you get so dramatic an impact as embryonic lethality.
Have you characterized the transgene insertion sites? Most transgenic mice are not genetically stable and they may show instable phenotypes after several generations.
Transgenic or not doesn't seem to be the issue- the phenotype you mention could result from a variety of factors combining to cause embryonic lethality (i.e. it could be several orders removed from the gene directly targeted, or require other input as in synthetic lethality). As others mentioned, breeding efficacy certainly does fluctuate with seasons, in many strains of mice. Unpublished observations from the lab of my thesis advisor (Al Malkinson)- mouse metabolism of certain carcinogens (but not all) decreases dramatically during April, such that similar doses administered at just about any other time of the year yield several times-more tumors. This was not observed with carcinogens requiring CYP2E1 metabolism, but was for CYP1A and CYP2B. This is entirely anecdotal of course. Just as Margit pointed out, the mice do not live under absolutely constant conditions because of their interactions with you, the experimenter, and the animal care staff, and the air, despite HEPA-quality filtration. Which probably have pets, as well, which may transfer scents or hormones to the clothing/scrubs/ undergarments/hair as they come into the facility...
Expect seasonal changes in breeding performance. Some strains produce more litters in the spring and summer than in winter and fall.
First of all thanks to everybody for your input, I really appreciate all of it very much!
Obviously many people working with mice notice these phenomena, whereas not so much is visible in literature about it. In our case the knockout mice might be slightly more sensitive to certain kinds of stress compared to wild-type controls, which eventually translates into lower viability in embryogenesis. This stress seems to be higher in fall/winter than in summer.
The existence of "circannual clock genes" as mentioned by Bogdan I find extremely facinating, even more if they keep on cycling without the major cues present in nature (at least as sensed by us humans) ;-)
Best wishes,
Andreas
I noticed higher breeding performance during spring and fall and lower during fall and winter. Some strains are more susceptible than others. Despite the "controlled" environment, the mice still have their biological clock.
Good luck
Agnes
When I was trained to work with mice, the Post Doc who trained me mentioned that mice sometimes have lower breeding in very humid weather, even in controlled environments. I'll see how that pans out for me living here in Louisiana. Then again, two of my strains of mice have questionable parenting skills.