Enhancing human ACE2 expression in mouse models to improve COVID‐19 research DOI Creative Commons

Sun Jiaoyang,

Cheng Shaofei,

Hong Guangliang

и другие.

FEBS Open Bio, Год журнала: 2024, Номер 15(2), С. 324 - 334

Опубликована: Дек. 29, 2024

Mice are one of the most common biological models for laboratory use. However, wild-type mice not susceptible to COVID-19 infection due low affinity mouse ACE2, entry protein SARS-CoV-2. Although with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit expression, potentially limiting their fidelity in mimicking manifestations and utility viral studies. Here, we created compared hACE2 generated different strategies. Our findings show that distinct β-globin insertion within cassette significantly influences downstream placement enhancing transcription. Moreover, optimizing codons (opt-hACE2) improves translation efficiency multiple tissues. Notably, opt-hACE2 displayed more active immune responses severe phenotypes following SARS-CoV-2 challenge other models. study demonstrates dual regulatory role element transgene transcription suggests might serve as valuable tools research.

Язык: Английский

FrozONE: quick cell nucleus enrichment for comprehensive proteomics analysis of frozen tissues DOI Creative Commons

Lukas A Huschet,

Fabian P. Kliem,

P. Wienand

и другие.

Life Science Alliance, Год журнала: 2024, Номер 8(3), С. e202403130 - e202403130

Опубликована: Дек. 12, 2024

Subcellular fractionation allows for the investigation of compartmentalized processes in individual cellular organelles. Nuclear enrichment methods commonly employ use density gradients combined with ultracentrifugation freshly isolated tissues. Although it is broadly used combination proteomics, this approach poses several challenges when comes to scalability and applicability frozen material. To overcome these limitations, we developed FrozONE (Frozen Organ Nucleus Enrichment), a nucleus proteomics workflow By extensively benchmarking our against alternative methods, showed that faster, simpler, more scalable conventional methods. allowed study, profiling, classification nuclear proteomes different tissues complex heterogeneity, ensuring optimal from cell types quantitative resolution low abundant proteins. In addition its performance healthy mouse tissues, proved be very efficient characterization liver proteome alterations pathological condition, diet-induced nonalcoholic steatohepatitis.

Язык: Английский

Процитировано

0
Enhancing human ACE2 expression in mouse models to improve COVID‐19 research DOI Creative Commons

Sun Jiaoyang,

Cheng Shaofei,

Hong Guangliang

и другие.

FEBS Open Bio, Год журнала: 2024, Номер 15(2), С. 324 - 334

Опубликована: Дек. 29, 2024

Mice are one of the most common biological models for laboratory use. However, wild-type mice not susceptible to COVID-19 infection due low affinity mouse ACE2, entry protein SARS-CoV-2. Although with human ACE2 (hACE2) driven by Ace2 promoter reflect its tissue specificity, these animals exhibit expression, potentially limiting their fidelity in mimicking manifestations and utility viral studies. Here, we created compared hACE2 generated different strategies. Our findings show that distinct β-globin insertion within cassette significantly influences downstream placement enhancing transcription. Moreover, optimizing codons (opt-hACE2) improves translation efficiency multiple tissues. Notably, opt-hACE2 displayed more active immune responses severe phenotypes following SARS-CoV-2 challenge other models. study demonstrates dual regulatory role element transgene transcription suggests might serve as valuable tools research.

Язык: Английский

Процитировано

0