{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe ru2(d) allele, which results from a frameshift mutation in the Hps5 gene, disrupts normal melanocyte differentiation. Studies have shown that melanoblasts from mutant mice proliferate normally but fail to effectively differentiate into mature melanocytes due to markedly reduced tyrosinase activity and decreased expression of key melanogenic enzymes (TYR, TRP1, and TRP2). This impaired differentiation can be rescued by supplementation with excess L‑tyrosine, underscoring the role of substrate availability in overcoming the defect."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Disruption of normal melanocyte maturation by the ru2(d) allele leads to selective inhibition of eumelanin synthesis, resulting in a marked reduction of eumelanin in both the epidermis and hair of affected mice. In contrast, pheomelanin synthesis appears to be less affected—and in some circumstances even enhanced—suggesting that the mutation differentially modulates the two distinct melanin synthetic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "In addition to its role in pigment production, the Hps5 mutation underlying the ru2(d) allele may have broader physiological consequences. The mutation is also associated with systemic alterations, as evidenced by the spontaneous occurrence of hypopigmentation along with features such as chronic diarrhea and granulomatous colitis, making this model valuable for studying the links between pigmentation disorders and inflammatory bowel diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomohisa Hirobe, Chihiro Yoshihara, Sakae Takeuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel deletion mutation of mouse ruby-eye 2 named ru2(d)/Hps5(ru2-d) inhibits melanocyte differentiation and its impaired differentiation is rescued by L-tyrosine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zoolog Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2108/zsj.28.790"}], "href": "https://doi.org/10.2108/zsj.28.790"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22035301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22035301"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomohisa Hirobe, Kazumasa Wakamatsu, Shosuke Ito "}, {"type": "b", "children": [{"type": "t", "text": "A new mutation of mouse ruby-eye 2, ru2(d)/Hps5(ru2-d) inhibits eumelanin synthesis but stimulates pheomelanin synthesis in melanocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zoolog Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2108/zsj.29.652"}], "href": "https://doi.org/10.2108/zsj.29.652"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23030338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23030338"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tomohisa Hirobe, Shosuke Ito, Kazumasa Wakamatsu "}, {"type": "b", "children": [{"type": "t", "text": "The mouse ruby-eye 2(d) (ru2(d) /Hps5(ru2-d) ) allele inhibits eumelanin but not pheomelanin synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pigment Cell Melanoma Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/pcmr.12118"}], "href": "https://doi.org/10.1111/pcmr.12118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23672590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23672590"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yumi Itoh, Yasuo Nagaoka, Yoshio Katakura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Simple chronic colitis model using hypopigmented mice with a Hermansky-Pudlak syndrome 5 gene mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pigment Cell Melanoma Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/pcmr.12504"}], "href": "https://doi.org/10.1111/pcmr.12504"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27333462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27333462"}]}]}]}