International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 79 - TRANSGENIC MICE EXPRESSING HUMAN ZAC, A CANDIDATE GENE FOR THE IMPRINTED DISORDER TNDM

Dr. Gavin Kelsey
MRC Senior Fellow
The Babraham Institute
Developmental Genetics Programme
Cambridge CB2 4AT
United Kingdom

Co-Authors: Ma D, Smith RJ, Arnaud P, Konfortova G, Dean WL
Institutions: Developmental Genetics Programme, The Babraham Institute

As the result of a methylation-based screen for imprinted genes in the mouse, we identified Zac1 as an imprinted gene with paternal expression. The Zac1 CpG island has maternal-allele methylation and may be involved in controlling imprinting of the locus, as methylation is present in oocytes but not sperm. Zac1 encodes a zinc finger protein which promotes apoptosis and cell cycle arrest. The gene resides on Chr. 10, a chromosome without recognised imprinting effects. The human homologue (6q24-q25) is a candidate for the imprinted disorder transient neonatal diabetes mellitus (TNDM). TNDM is a developmental disease of insulin production, characterized by intrauterine growth retardation, insulin dependence in infants and a 60% risk of developing permanent diabetes. TNDM occurs with paternal duplication of 6q, implicating overexpression of ZAC in the disease mechanism. Uniparental disomy for mouse Chr. 10 is not associated with a phenotype similar to TNDM. To account for this phenotypic discrepancy and investigate a potential animal model for TNDM, transgenic mice with PACs containing human ZAC have been made. In all transgenic lines examined, human ZAC is imprinted. RT-PCR and in situ analyses show that offspring from transgenic males express human ZAC widely, including the pancreas, pituitary and adrenal gland. Further work will examine blood glucose homeostasis, pancreatic beta cell function and apoptosis in this transgenic model.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012