Tyr is the mouse gene that encodes tyrosinase, an enzyme that triggers the first and rate‐limiting step in the biosynthesis of melanin. Mutations in Tyr might result in non‐functional Tyr protein and, consequently, loss of pigment production. This is a rare genetic condition, known as albinism, described for most animal species and one of the most obvious and simple phenotypes to investigate in model organisms. Mutations in the orthologous human TYR gene are associated with oculocutaneous albinism type 1 (OCA1). Over the last thirty years, the mouse Tyr locus has been studied as a paradigm for how genes and expression domains are organized and regulated in mammalian genomes. This review summarizes the major findings and experimental strategies used, from the production of conventional transgenic mice to the latest CRISPR‐Cas9 genome‐edited animals. The main conclusion inferred from all of these studies, which extends beyond the analysis of the mouse Tyr locus, is the relevance of analyzing non‐coding regulatory DNA elements in their natural chromosomal environment, and not only as randomly inserted transgenes. Further, the identification of evolutionary conserved regulatory sequences might highlight new vulnerable sites in the human TYR gene, whose mutations could also be associated with albinism.

中文翻译：

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小鼠酪氨酸酶基因座的结构和功能

Tyr是编码酪氨酸酶的小鼠基因，酪氨酸酶是触发黑色素生物合成的第一步和限速步骤的酶。Tyr 的突变可能会导致无功能的 Tyr 蛋白，从而导致色素生成损失。这是一种罕见的遗传病，称为白化病，对大多数动物物种都有描述，也是在模型生物中研究的最明显和最简单的表型之一。直系同源人类TYR基因的突变与 1 型眼皮肤白化病 (OCA1) 相关。在过去的三十年里，老鼠Tyr基因座已被研究作为哺乳动物基因组中基因和表达域如何组织和调节的范例。本综述总结了主要发现和使用的实验策略，从传统转基因小鼠的生产到最新的 CRISPR-Cas9 基因组编辑动物。从所有这些研究中推断出的主要结论超出了对小鼠Tyr基因座的分析，是分析其天然染色体环境中的非编码调节 DNA 元件的相关性，而不仅仅是作为随机插入的转基因。此外，进化保守调控序列的鉴定可能会突出人类TYR基因中新的脆弱位点，其突变也可能与白化病有关。