The mouse resource at National Resource Center for Mutant Mice.

Mouse models are essential for dissecting disease mechanisms and defining potential drug targets. There are more than 18,500 mouse strains available for research communities in National Resource Center for Mutant Mice (NRCMM) of China, affiliated with Model Animal Research Center of Nanjing University and Gempharmatech Company. In 2019, Gempharmatech launched the Knockout All Project (KOAP) aiming to generate null mutants and gene floxed strains for all protein-coding genes in mouse genome within 5 years. So far, KOAP has generated 8,004 floxed strains and 9,769 KO (knockout) strains (updated to Oct, 2021). NRCMM also created hundreds of Cre transgenic lines, mutant knock-in models, immuno-deficient models, and humanized mouse models. As a member of the international mouse phenotyping consortium (IMPC), NRCMM provides comprehensive phenotyping services for mouse models. In summary, NRCMM will continue to support biomedical community with new mouse models as well as related services.

Water quality and health risk assessment of the water bodies in the Yamdrok-tso basin, southern Tibetan Plateau.

Water resources in good quality guarantee the primary condition for the maintenance and development of the natural ecosystem and human society. Water quality status and health risk of the lake water bodies in the national nature reserve, the Yamdrok-tso basin, in the southern Tibetan Plateau are assessed by 25 water parameters including 12 heavy metal(loid)s. Results reveal that the lake water bodies possess relatively high pH (9.68), high concentrations of F (1.66 mg/L), Cu (13.92 µg/L), As (41.60 µg/L), Pb (26.69 µg/L), and U (19.53 µg/L), and a low value of dissolved oxygen (19.30%). The pollution indices (heavy metal pollution index of 0.88-22.88, heavy metal evaluation index of 0.18-3.75, and the degree of contamination of -8.82 to -5.25) demonstrate that the lake water bodies are in a low pollution level with respect to heavy metal(loid)s. The evaluation of water quality based on the fuzzy comprehensive assessment method suggests that 75.56% of the water samples meet the regulation of the China National Standard for water resources in national nature reserves. Health risk assessment shows that potential hazards exist on this region when the residents under long-term exposure to the lake water through oral and dermal pathways, of which children and adults are mostly exposed to As and F for non-carcinogenic and As for carcinogenic risks, especially for children. Results of this study contribute to targeted water resources management in the national nature reserves.

A Small Indel Mutant Mouse Model of Epidermolytic Palmoplantar Keratoderma and Its Application to Mutant-specific shRNA Therapy.

Epidermolytic palmoplantar keratoderma (EPPK) is a relatively common autosomal-dominant skin disorder caused by mutations in the keratin 9 gene (KRT9), with few therapeutic options for the affected so far. Here, we report a knock-in transgenic mouse model that carried a small insertion-deletion (indel) mutant of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), corresponding to the human mutation KRT9/c.500delAinsGGCT (p.Tyr167delinsTrpLeu), which resulted in a human EPPK-like phenotype in the weight-stress areas of the fore- and hind-paws of both Krt9(+/mut) and Krt9(mut/mut) mice. The phenotype confirmed that EPPK is a dominant-negative condition, such that mice heterozygotic for the K9-mutant allele (Krt9(+/mut)) showed a clear EPPK-like phenotype. Then, we developed a mutant-specific short hairpin RNA (shRNA) therapy for EPPK mice. Mutant-specific shRNAs were systematically identified in vitro using a luciferase reporter gene assay and delivered into Krt9(+/mut) mice. shRNA-mediated knockdown of mutant protein resulted in almost normal morphology and functions of the skin, whereas the same shRNA had a negligible effect in wild-type K9 mice. Our results suggest that EPPK can be treated by gene therapy, and this has significant implications for future clinical application.