Shibahara S, Okinaga S, Tomita Y, Takeda A, Yamamoto H, Sato M, Takeuchi T
Department of Applied Physiology, Tohoku University School of Medicine, Sendai, Japan.
Eur J Biochem. 1990 Apr 30;189(2):455-61. doi: 10.1111/j.1432-1033.1990.tb15510.x.
Murine albinism is characterized by complete lack of melanin pigments in skin and retina. In order to study the molecular basis of albinism, we have cloned and characterized the tyrosinase gene of BALB/c mice (c/c). Sequence analysis of this gene reveals a point mutation at nucleotide residue 387 (G----C transversion) causing a Cys----Ser substitution at position 85 in one of the cysteine-rich domains of the tyrosinase molecule. Since this G----C transversion creates an additional DdeI site, we were able to confirm that this mutation is actually present in BALB/c genomic DNA using DNA amplification techniques. In contrast, both C57BL/6 (C/C) and DBA/2 (C/C) mouse strains carry the G residue at the same position, suggesting that this point mutation is specific for the albino mutation at the c locus. Moreover, we were able to show that the tyrosinase containing Ser-85 is not functional in transient expression of its cDNA. We therefore suggest that a G----C transversion at nucleotide residue 387 of the tyrosinase gene could lead to the albino phenotype of BALB/c mouse.
小鼠白化病的特征是皮肤和视网膜中完全缺乏黑色素。为了研究白化病的分子基础，我们克隆并鉴定了BALB/c小鼠（c/c）的酪氨酸酶基因。对该基因的序列分析揭示了核苷酸残基387处的一个点突变（G→C颠换），导致酪氨酸酶分子富含半胱氨酸结构域之一中第85位的半胱氨酸被丝氨酸取代。由于这种G→C颠换产生了一个额外的DdeI位点，我们能够使用DNA扩增技术证实该突变实际上存在于BALB/c基因组DNA中。相比之下，C57BL/6（C/C）和DBA/2（C/C）小鼠品系在相同位置都携带G残基，这表明该点突变是c位点白化病突变所特有的。此外，我们能够证明含有Ser-85的酪氨酸酶在其cDNA的瞬时表达中无功能。因此，我们认为酪氨酸酶基因核苷酸残基387处的G→C颠换可能导致BALB/c小鼠的白化病表型。
