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 females were born and developed as any normal mouse, but were ten percent smaller than wild type mice. When the fosB homozygous females were mated with fosB homozygous mutant males, the resulting pregnancies were normal and carried to term. However, twenty-four to fourty-eight hours after delivery, the mortality rate of the pups was in excess of fifty percent. The high occurrance of lethality could be attributed to either the mutant mothers, the mutant pups, or both. To isolate the cause of the high mutant pup mortality rate, heterozygous males were mated with homozygous females and vice versa. As a result, it was found that the number of surviving pups in any given pregnancy relied primarily upon the genotype of the mother, and was independent of father or pup genotype. This supports the idea that the survival relies heavily on the nurturing ability of the fosB mothers.
Physical Trait Analysis:
To isolate the defect in the mother that contributed to the death of her pups, a physical trait analysis was performed. The most obvious mechanism leading to pup mortality would be a postnatal lactation defect in the mammary glands. 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.
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;...