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

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POSTER 95 - GLOBAL DYSREGULATION OF NORMAL GENE EXPRESSION PATTERNS IN PLACENTAS OF CLONED MICE

Dr Hiroshi Suemizu
Central Institute for Experimental Animals
1430 Miyamae, Nogawa
Kawasaki 216-0001
Japan

Co-Authors: 1) Shimozawa N, 1) Tamaoki  N, 2) Aiba K, 2) Ko SHM
Institutions: 1) Central Institute for Experimental Animals  2) Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH

Increased placental and birth weights are the most common abnormalities of cloned animals generated by the transfer of somatic nuclei. It has been speculated that this phenotype, called 'large offspring syndrome,' is caused by the dysregulation of control of gene expression. However, investigations have thus far been limited to the analyses of several imprinted genes and the methylation status of genomic DNA. To gain further perspective on the extent of changes, we have carried out gene expression profiling on cloned mouse placentas using the NIA 15K mouse cDNA microarray. Here we report four principal features: (1) inappropriate expression of imprinted genes, including a ~10-fold reduction of H19 levels; (2) overexpression of genes involved in placental growth; (3) increased expression of oncogenes and growth promoting genes; and (4) alteration of regulatory proteins involved in global gene expression, such as DNA methyltransferase and histone acetyltransferase. Our results indicate that placentomegaly in cloned animals is caused by large-scale dysregulation of normal gene expression as well as the dysregulation of imprinted genes.