A Defect in Nurturing in Mice Lacking the Immediate Early Gene FosB

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Background to the Project

In early 1995, an M.D-Ph.D student, Jennifer Brown, was breeding mice with an inactivated form of the gene FosB. With the inactivation of the gene, healthy pups from the mutated mice died quickly. Observing this occurrance, Brown found that the mother mice ignored her offspring. From this discovery, Brown proposed that the inactivation of the immediate early gene FosB causes a defect in the nurturing behaviors of female mice. To prove this, Brown bred a series of knockout mice with the inactivated FosB gene. She then observed the nurturing behaviors of the knockout mice and compared them to those of the normal mice.

The Test Results

FosB Mutant Development and Abnormalities:

FosB mutant homozygous
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Comparing the mammary glands of the FosB mutant mothers with those of the wild-type mothers, no discernable differences were found. Initially, the mutant mothers failed to lactate postpartum. However, this was due to her failure to nurse the pups and not a physical defect in the mammary glands manifesting from the FosB mutation. In subsequent examinations, the reproductive tracts, hormonal status, and gross anatomy of the pituitary and hypothalmus were investigated. No obvious physical or anatomic abnormalities were found in the FosB mutants that would explain the postnatal pup lethality.

Behavioral Analysis:

After ruling out any physical abnormalities, an explanation concerning some sort of behavioral defect was sought; namely one considering postnatal care of the pups. After birth, it was immediately noted that mutant mothers failed to exhibit normal nurturing behavior: creating a nest, cleaning the pups, retrieving them to the nest, and crouching over them for warmth and nursing. The mutant mothers, rather, sat in a corner and ignored the pups that were scattered around the cage; failing to collect them or huddle over them to keep them warm.

Behavioral Testing:

To identify any behavioral defects, the mutant mothers were subjected to a series of tests.

TEST ONE:

The mothers (normal and mutant) were exposed to their pups for 20 minutes after birth before the cages were disturbed.

The normal mothers spent this time

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