Evidence map›Paper›PMID 40556005›Full record

ArticleCell & bioscience2025

FRRS1L variants and ferriheme overload drive hyperpigmentation and systemic Iron overload in lanping black bone sheep.

Deping Han, Yuanyuan Zhang, Weidong Deng, Xue Yang, Jianfei Chen, Guoying Hua, Hesham Y A Darwish, Huaming Mao, Xiao Gou, Jiankui Wang and 10 more

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In one paragraph

Article in Cell & bioscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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5 · Who and what money

Authors and funding

20 authors.

Deping Han *Animal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Yuanyuan Zhang *Animal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Weidong DengFaculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Xue YangAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Jianfei ChenAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Guoying HuaAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Hesham Y A DarwishAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Huaming MaoFaculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Xiao GouFaculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Jiankui WangAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Kai CuiAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Yuhao MaAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Yurong TaiAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Xianggui DongAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Yanzhu YaoAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Zu YangAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Suying CaoBeijing University of Agriculture, Animal Science and Technology College, Beijing, 100096, China.
Zhengquan YuAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China.
Wansheng LiuDepartment of Animal Science, Center for Reproductive Biology and Health, College of Agricultural Sciences, The Pennsylvania State University, University Park, 16802, PA, USA. wul12@psu.edu.
Xuemei DengAnimal Genetics, Breeding, and Reproduction of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, 100193, China. deng@cau.edu.cn.ORCID http://orcid.org/0000-0003-1759-6499

Funding

2115 Talent Development program of China Agricultural University 2115 Talent Development program of China Agricultural UniversityBiological Breeding-National Science and Technology Major Project 2023ZD040750XNational Natural Science Foundation of China U1136605
6 · The paper itself

Abstract

backgroundHemoglobin metabolism disorder can result in systemic iron overload, leading to pigmentation in multiple organs. Although these disorders are often of genetic origin, the specific genes and mechanisms remain incompletely understood. Lanping black bone sheep (LP–BBS), a unique population from the high altitudes along the Hengduan Mountains in Yunnan province, exhibits hyperpigmentation in multiple tissues. Investigating the genetic and environmental factors underlying this phenotype provides a natural model to better understand hemoglobin metabolism disorder.

resultsLP-BBS were found to exhibit increased red blood cell counts, elevated hemoglobin levels, and systemic iron overload, evidenced by hyperpigmentation in various tissues. Histological and molecular analyses revealed that hyperpigmentation is driven by ferriheme overload, an inheritable quantitative trait influenced by both genetic variation and environmental factors. Genome-wide association studies identified FRRS1L as a candidate gene, with significant mutations in its 3′-untranslated region (3′-UTR) reducing FRRS1L expression. Functional assays demonstrated that insufficient FRRS1L expression promotes ferriheme accumulation in reticuloendothelial cells and macrophages, as confirmed in vitro using FRRS1L knockdown models. Ferriheme overload was associated with oxidative stress and systemic inflammation, causing pathological damage to critical organs such as the kidney, liver, and uterus.

conclusionThis study identifies FRRS1L as a key contributor to ferriheme overload through aberrant hemoglobin metabolism in LP–BBS. These findings offer new insights into the genetic basis and pathological mechanisms of iron overload disorders, providing a potential target for therapeutic intervention. Moreover, LP–BBS serves as a valuable natural model for studying hematogenous pigment disorders and their interplay with environmental factors.

Indexed as

Black bone sheepHyperpigmentationIron overloadMacrophageSystemic inflammation

Identifiers

PMID40556005
PMCPMC12188663

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