International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


X Du
The Scripps Research Institute

Whitten C, Mann N, Beutler B
The Scripps Research Institute

Maternal acceptance of the trophoblast—a “semi-allograft” by virtue of its content of paternal genes—is one of the central mysteries of immunology.  While most tissue allografts (e.g. transplanted organs) are rejected by the adaptive immune system, the placenta provokes essentially no immune response.  Disruption of the system for maternal tolerance should produce a state of selective allogeneic sterility, and ENU is being used to create female mice with germline mutations that produce this phenotype.  F1 and F3 C57BL/6J females with germline mutations are enrolled in a screen to detect mutations that disrupt maternal tolerance.  In detail, female mice are first outcrossed with C3H/HeN males.  Within 90 days of exposure to an allogeneic male, 99% of normal mice have undergone parturition.   Any mutant mouse that has been exposed to a C3H/HeN male for more than 90 days without achieving parturition is enrolled in a syngeneic cross.  Syngeneically sterile females are discarded, while syngeneically fertile females are again crossed to C3H/HeN males to confirm allogeneic sterility.  Female mice that show selective allogeneic sterility are considered to be potential hits.  Their syngeneic offspring are tested for heritance of the trait. To date, 3800 F1 and 3900 F3 mice have been screened in this manner.  We consider that functional inactivation of approximately 12% of the genome has been achieved in the F3 generation.

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