Evidence map›Paper›PMID 31720743›Full record

ArticleCellular and molecular life sciences : CMLS2020

Genetic deletion of a short fragment of glucokinase in rabbit by CRISPR/Cas9 leading to hyperglycemia and other typical features seen in MODY-2.

Yuning Song, Tingting Sui, Yuxin Zhang, Yong Wang, Mao Chen, Jichao Deng, Zhonglin Chai, Liangxue Lai, Zhanjun Li

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 23 citations in OpenAlex.

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  9. CRISPR: A new paradigm of theranostics.Nanomedicine : nanotechnology, biology, and medicine · 2021
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  11. Functional Inactivation ofInternational journal of molecular sciences · 2021
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  12. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Yuning SongJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.
Tingting SuiJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.
Yuxin ZhangJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.
Yong WangJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.
Mao ChenJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.
Jichao DengJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.
Zhonglin ChaiDepartment of Diabetes, Central Clinical School, Pathophysiology of Diabetic Complications Laboratory, Monash University, Melbourne, Australia.
Liangxue LaiJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China. lai_liangxue@gibh.ac.cn.
Zhanjun LiJilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China. lizj_1998@jlu.edu.cn.ORCID http://orcid.org/0000-0001-6914-8589
Jilin University · CNMonash University · AU

Funding

China Postdoctoral Science Foundation Funded Project 2018M641784China Postdoctoral Science Foundation Funded Project 2019T120236Guangdong Province science and technology plan project 2014B020225003the National Key Research and Development Program of China Stem Cell and Translational Research 2017YFA0105101The Strategic Priority Research Program of the Chinese Academy of Sciences XDA16030501The Strategic Priority Research Program of the Chinese Academy of Sciences XDA16030503
6 · The paper itself

Abstract

Glucokinase (GCK) is a key enzyme in glucose sensing and glycemic regulation. In humans, mutations in the GCK gene cause maturity-onset diabetes of the young 2 (MODY-2), a disease that is characterized by an early-onset and persistent hyperglycemia. It is known that Gck knockout (KO) is lethal in mice with Gck KO mice dying within 2 weeks after birth. Therefore, Gck KO mice are not suitable for preclinical study and have limited suitability to study the pathophysiological role of glucokinase in vivo. Here, we report the generation of a novel rabbit with a non-frameshift mutation of GCK gene (GCK-NFS) by cytoplasm microinjection of Cas9 mRNA and gRNA. These GCK-NFS rabbits showed typical features of MODY-2 including hyperglycemia and glucose intolerance with similar survival rate and weight compared to wild-type (WT) rabbits. The diabetic phenotype including pancreatic and renal dysfunction was also found in the F1-generation rabbits, indicating that the genetic modification is germline transmissible. Treatment of GCK-NFS rabbit with glimepiride successfully reduced the fasting blood glucose drastically and improved its islet function. In conclusion, this novel GCK mutant rabbit generated with the CRISPR/Cas9 system mimics most, if not all, histopathological and functional defects seen in MODY-2 patients such as hyperglycemia and will be a valuable rabbit model for preclinical studies and drug screening for diabetes as well as for studying the pathophysiological role of glucokinase.

Indexed as

AnimalsBlood GlucoseCRISPR-Cas SystemsDiabetes Mellitus, Type 2Gene DeletionGlucokinaseHumansHyperglycemiaMiceMice, KnockoutMutationPhenotypeRabbitsBlood GlucoseGlucokinaseCRISPR/Cas9GlucokinaseMODY-2 typePreclinical testingRabbit

Identifiers

PMID31720743
PMCPMC11105094
OpenAlexW2986598799

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.