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The reproducibility of research using laboratory animals requires reliable management of their quality, in particular of their genetics, health and environment, all of which contribute to their phenotypes. The point at which these biological materials are transferred between researchers is particularly sensitive, as it may result in a loss of integrity of the animals and/or their documentation. Here, we describe the various aspects of laboratory animal quality that should be confirmed when sharing rodent research models. We also discuss how repositories of biological materials support the scientific community to ensure the continuity of the quality of laboratory animals. Both the concept of quality and the role of repositories themselves extend to all exchanges of biological materials and all networks that support the sharing of these reagents. [ABSTRACT FROM AUTHOR]

The mouse tyrosinase gene, encoding the rate-limiting enzyme in the melanin synthesis pathway, was assigned, in 1990, to the c (albino ) locus by classical rescue experiments driven by functional constructs in transgenic mice. These pioneer reports triggered the study of the regulation of endogenous tyrosinase gene expression by combining different amounts of upstream regulatory and promoter regions and testing their function in vivo in transgenic animals. Indeed, the expression studies on the mouse tyrosinase gene regulation have eventually become an example and, possibly, a paradigm of how a representative mammalian expression domain could be organized within the nuclear chromatin, and how a gene establishes its specific pattern of expression during development and throughout the life of an organism. Correct and reproducible tyrosinase transgenic expression was not achieved in the initial studies. In contrast, faithful tyrosinase transgenic expression was reported when the entire expression domain was transferred to the germ-line of mice using artificial-chromosome-type transgenes. The use and modification of these large tyrosinase transgenic constructs enabled the discovery of previously unknown but fundamental regulatory regions, such as the tyrosinase locus control region (LCR), whose presence was required in order to guarantee position independent and copy number dependent-expression of tyrosinase transgenes, with an expression level, per copy, comparable to that of an endogenous wild-type allele. Subsequently, functional dissection of regulatory elements present within this LCR through the generation of new artificial-chromosome type tyrosinase transgenes have revealed the existence of different regulatory activities, including the description of a novel boundary element. New in vivo and in vitro studies have contributed to establish the relevance of the regulatory elements associated with the mouse tyrosinase expression domain. The presence of some of these elements has also been identified in other mammalian species by genome comparison analysis, thus indicating the evolutionary importance of their presence in tyrosinase genes (and transgenes). [ABSTRACT FROM AUTHOR]

Albinos display abnormal pigment synthesis, a defect arising from the absence or reduction in melanin synthesis, as in Oculo-Cutaneous Albinism Type I (OCA1), where tyrosinase is defective. Congenital defects in retinal pigmentation result in visual abnormalities affecting the retina and pathways into the brain. Albinos have a deficit in photoreceptor rod numbers, abnormal ganglion cell layer in the central retina and misrouted chiasmatic pathways. Transgenic animals expressing a functional tyrosinase gene on an albino genetic background display a correction of all these abnormalities. These results strongly suggested a direct or indirect implication of tyrosinase in the normal development of the mammalian retina. Mammalian retinal development requires a complex set of genetic events during embryogenesis. We have generated a transgenic mouse model with inducible expression of the tyrosinase gene to address the function of tyrosinase in establishing normal retinal architecture. We have produced two types of transgenic mice: first, mice expressing the transactivator rtTA (tetracycline system, tet-on ) chimeric protein under the control of tyrosinase promoter and Locus Control Region (LCR), and; second, transgenic mice expressing a mouse tyrosinase cDNA construct driven by a minimal promoter inducible by rtTA in the presence of doxycycline. Double transgenic lines have been selected according to the maximum activation of the tyrosinase-rtTA transgenes as measured with reporter transgenic mice. Inducible experiments have been carried out with selected double transgenic mouse lines. Tyrosinase expression has been triggered from its normal time (+9.5 dpc) of embryo development, by exposing the animals to doxycycline in drinking water, and the effects of the induction of this gene evaluated by histological and biochemical methods in heterozygous and homozygous double transgenic individuals. We have observed an increase of tyrosinase activity in induced animals, as compared to littermate controls. However, a significant interindividual variability has also been recorded in these animals, as it has been reported in analogous experiments. These mice could be instrumental to reveal critical temporal windows for tyrosinase expression resulting in normal retinal development. [ABSTRACT FROM AUTHOR]