Stirling, Lucy Caroline; (2004) Generation and characterisation of a nociceptor specific Cre expressing mouse. Doctoral thesis (Ph.D), UCL (University College London).

Text Generation_and_characterisatio.pdf Download (14MB)

Abstract

Examination of mouse null mutants provides useful insights into gene function, but perinatal lethality or developmental compensatory mechanisms may obscure behavioural phenotypes. The bacteriophage Cre-loxP system provides a method of producing deletion of genes in specific tissue. The tetrodotoxin-resistant voltage gated sodium channel, Nav1.8, is expressed exclusively in a subset of primary afferent neurons, more than 85% of which are nociceptors. The heterozygous Nav1.8 mouse has been shown to have a normal electrophysiological and behavioural phenotype. In this project gene targeting was used to insert the Cre-recombinase gene into the translational start of Nav1.8 in embryonic stem cells and transgenic mice expressing Cre under the control of the Nav1.8 promoter were generated. The expression pattern of functional Cre was examined using ROSA26 reporter mice and was found to be identical to Nav1.8. Expression started at E13 and was limited to small diameter neurons in dorsal root ganglia, trigeminal ganglia and nodose ganglia. There was no expression in non-neuronal cells or in the central nervous system. This pattern of expression did not alter in adult animals. Examination of the Nav1.8 mediated TTX-resistant current in small diameter dorsal root ganglion neurons from heterozygote Nav1.8Cre animals revealed that it was identical to that in wild type neurons. In addition, the nociceptive behavioural phenotype of adult heterozygote Nav1.8Cre mice both in tests of mechanical and thermal thresholds and in models of inflammatory and neuropathic pain, was identical to that of wild type mice. These findings demonstrate that the Nav1.8Cre mouse line is a suitable tool to examine the effects of nociceptor specific gene deletion on pain behaviour, and so provide insights into the role of widely expressed genes in nociception.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item