Human Reproduction, Vol. 14, No. 8, 1927-1939,
August 1999
© 1999 European Society of Human Reproduction and Embryology
Debates |
Manipulating the genome to study reproduction
Mice with `humanized' zonae pellucidae
1 Laboratory of Cellular and Developmental Biology, NIDDK, Building 6, Room B 126,National Institutes of Health, Bethesda, MD 20892, USA
The current revolution in biology has provided new insights into mechanisms of mammalianprocreation. However, detailed knowledge of the molecular basis of human reproduction remainslimited because of ethical, regulatory, and societal considerations. Although non-human primates are closely related and can serve as valuable models of human biology, cost and care of primate colonies are formidable and beyond the means of many investigators. Thus, development of small animal models that more closely approximate human reproduction is highly desirable.
Human genes can be introduced into mice using a variety of methodologies (Cohen-Tannoundji and Babinet, 1999
). One approach is to establish homozygous `knockout' mouse lines from embryonic stem cells in which the gene of interest has been inactivated by insertional mutagenesis. This line can be crossed with a second transgenic line that expresses the homologous human protein. The flexibility of this approach lies in the ability to rescue the `null' phenotype with either
Molecular basis of mammalian fertilization
Immunocontraceptive development
Autoimmune oophoritis and premature ovarian failure
Targeting pharmacological agents to the ovary
Future directions
Notes
References
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