International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

Mr Eric Anderson
SUNY Downstate Medical Center
Department of Biochemistry
450 Clarkson Avenue
Box 8
Brooklyn NY 11203 US

Co-Authors:  Jin DK and Feuerman MH
Institution:  Weill Medical College of Cornell University

Alpha-fetoprotein (AFP) is expressed in the yolk sac, fetal liver and gut and in the adult during liver regeneration and tumorigenesis.  AFP expression during liver regeneration is regulated by an unlinked, autosomal gene, Afr2.    A genetic polymorphism at this locus leads to 8- to 10-fold higher levels of AFP in C3H mice compared to C57BL/6 mice. Afr2 also regulates expression of H19, an untranslated mRNA regulating expression of Igf2.  Interestingly, C57BL/6 mice are less susceptible to liver tumorigenesis than are C3H/He mice, suggesting that AFP expression in regenerating liver may reflect other regulatory processes.

We have mapped Afr2 to mouse chromosome 2, ~75cM from the centromere by analysis of the progeny of a C3H x B6C3F1 backcross using MIT MapPair markers.  We have screened the RPCI-23 BAC library using these and other markers in this interval to identify BACs that map to the Afr2 locus.  Using fingerprinting and PCR techniques, we have made a ~1Mb BAC contig covering much of the Afr2 locus.  Upon completion, the BACs in this contig will be submitted to the Trans-NIH BAC sequencing program.  These BACs will be used in cDNA selection and exon trapping experiments to identify novel coding sequences in the Afr2 locus.  Genes mapped to the Afr2 locus or found on the human syntenic region (20p11-p13), will be screened for expression during liver regeneration, location within the contig and polymorphism between C3H and C57BL/6 mice.