Papillomas and carcinomas in transgenic rabbits carrying EJ-ras DNA and cottontail rabbit papillomavirus DNA

Abstract

Two transgenic rabbits (TRI and TRIII) that carried cottontail rabbit papillomavirus (CRPV) DNA alone were identified; another (TRII) carried both CRPV DNA and EJ-ras. TRI and TRIII developed extensive skin papillomas at about 1 month of age, and transcripts of CRPV DNA were detectable only in skin and/or papillomas. TRII developed extensive squamous carcinomas of the skin at a very early age. Transcription of both CRPV DNA and EJ-ras was found in the skin cancers. Thus, the tissue specificity of CRPV DNA expression in transgenic rabbits was the same as in virion-infected animals. The expression of EJ-ras could be dependent on the expression of certain CRPV genes and may be a critical cofactor of CRPV DNA in the progression of carcinomas.

Transgenic rabbit models for the study of atherosclerosis

“…The use of transgenic rabbit blood as a source of transgenic human "-1 antitrypsin was described by Massoud et al in 1990 (37), and a mouse monoclonal antibody gene was used to generate two transgenic rabbits by Weidle et al in 1991 (38). In 1993, Peng et al (39) described three interesting transgenic rabbits that were generated with rabbit papillomavirus DNA, in which the transgenic founders developed extensive squamous carcinomas of the skin at an early age. Fan et al (13) were the first to apply this technology to the study of lipid metabolism, and they have established several transgenic rabbit models for the study of atherosclerosis.…”

Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression

“…Since the first transgenic rabbit produced by Hammer and his colleagues 12 , transgenic rabbit models were generated by different laboratories worldwide for different research purposes, such as studies of lipid metabolism and atherosclerosis 13 14 15 16 17 18 , oncology 19 20 , acquired immunodeficiency syndrome (AIDS) 21 22 23 , and bioreactors for the production of pharmaceutical proteins 24 25 , However most of these rabbit models are produced by pronuclear microinjection of foreign DNA, in which the foreign genes are randomly inserted in the rabbit genome. This may be problematic as transgenes introduced into random sites within the rabbit genome are often subjected to position effects, including variations in the expression levels of the transgene caused by variation in the copy number of the transgenes or lack of crucial regulator elements related to the integration site, and potentially disrupting endogenous gene function through insertional mutagenesis.…”

Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus

“…In addition to different mutant viral genomes, rabbits with different genetic backgrounds (inbred, outbred, transgenic, and gene knockout) have been used to advance our understanding of the interaction of viral pathogenesis and host immunogenicity [7,33,[46][47][48][49][50][51][52][53][54]. In the current review, which is not inclusive of all of the research performed in the rabbit papillomavirus field, we focused on some of our recent findings relating to viral pathogenesis in the post-genetic modification era (Figure 1) and highlight recent advances in gene-modified rabbits [55] that can be used for future studies.…”