Now 2006A0115/2003A0097 -Stress, Infection and Antioxidant Systems

1,600 mice will be killed in these experiments. (800 knock out mice and 800 genetically matched wild type mice)
And in 2006 an additional 1,280 mice will be used. There is no change to the procedures.

In Their Own Words

It is hard to predict how the knock out animals will behave when infected or restraint stressed as they are perfectly normal under standard laboratory conditions. Our purpose is to determine whether the mice lacking various proteins involved in cellular antioxidant pathway demonstrate more sickness behavior compared to the wild type mice. The wild type C57/BL6 mice breathe heavily on day 5 onwards post infection. When infected with influenza A virus APR8 strain but they survive at least 12 to 15 days. (Meaning the mice are dead after that period.) It is possible that one or more of the knock out mice may manifest difficulty in breathing even before day 5 and they may not survive that long. If this is indeed the case it will implicate the role of the antioxidant protein in defence against the inflenza virus infection.

We will also determine whether these mice loose weight faster and consume less food that the C57/BL6 mice. If the animals are extremely sensitive to the influenza A virus infection and die within a few days of infection we will use a less virulent strain. Our collaborator Dr. Sheridan (see 01A0039 E Protocol) has stocks of these flu virus strains. ...If the animals exhibit severe respiratory distress, loose ability to move, eat or drink they will be euthanized immediately. In earlier collaborative study with Dr. Sheridan we infected IL-6 knock out mice with APR8 virus. These animals behaved like C57/BL6 mice although their gene expression profile was significantly altered. (Ghoshal, co-investigator for this protocol, Mol.Cell.Bio 2001

For the restraint study - "Animals will be restricted of movement each day for 12 hrs (6PM to 6AM) and this cycle will start one day prior to infection with the flu virus and will be repeated for five to seven days before the animals are sacrificed. We will observe the animals before we subject them to restraint stress and the animals will be monitored carefully each morning when they are released from the stress. (Who watches the mice while in the tube for 12 hours to insure they dont die in pain and distress? Oh yes this is an E protocol so it's okay.) If some animals appear to be sick as demonstrated by too much weight loss, inability to move, eat and drink, they will be euthanized. This study will be done in collaboration with Dr. John Sheridan. His lab does this type of studies for the past ten years."

Before reviewed by ILACUC, the principal investigator had wanted to restrain the mice for 16 hours - 5:00PM to 9:00AM.,which makes for better office hours for him. Who wants to get in the lab at 6:00AM to let out some mice out of a tube and see if they're still alive and kickin'.

And why is this study being conducted? "These studies will contribute to our understanding the role antioxidants (play) in health and disease." I believe nearly every day I read or see something about taking vitamin pills or eating the correct foods (with antioxidants) to keep us healthy.