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Title: Identification of candidate regulatory regions for insulin-like growth factor-2 imprinting on mouse distal chromosome 7
Author: Davies, K. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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The foetal growth gene Igf2 (Insulin-like growth factor 2) is imprinted and paternally expressed, and is located within a cluster of imprinted genes on mouse distal chromosome7, and an orthologous cluster on chromosome 11p15.5 in the human. Igf2 has important roles in foetal growth both in human and mouse, and is involved in the aetiology of human diseases, including the Beckwith-Wiedemann Syndrome (BWS) and some cancers. The aim of this research was to investigate further the regulatory mechanisms of parental imprinting within mouse distal chromosome 7, with particular interest in Igf2 regulation. In order to accomplish this, the imprinting status and gene structure of Kvlqt1 was investigated in mouse. Maternal expression of Kvlqt1 was demonstrated, together with the existence of several splice variants that differ to those found in human. Additionally, a new radiation induced imprint mouse mutation called Minute (Mnt) was analysed. This revealed that the Mnt mutation had arisen through an inversion downstream of H19, and results in the disruption of Igf2 expression in a tissue specific manner. Paternal transmission of Mnt abolishes Igf2 expression in a subset of mesodermal tissues (heart, lung and kidney) presumably through the disruption of the enhancers in these tissues, but Igf2 expression is retained in the other mesodermal tissues (skeletal muscle and tongue) and in endodermal tissues (liver and intestine). This provides evidence for the existence of at least three sets of enhancer elements, two of which (muscle enhancers and endoderm enhancers) are functional in Mnt mice. The characterisation of the mutation provided the likely location of the two sets of novel mesoderm enhancers within the cluster.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available