Neuroscience› Endocrine and Autonomic Systems› Regulation of Appetite and Obesity

Obesity and glucose metabolism — GPR21 receptor

Submitted 2026-10-23

Field: Neuroscience › Endocrine and Autonomic SystemsType: Couldn't replicate a published resultArea: obesity and glucose metabolismTarget: GPR21 receptorStage: preclinical

Hypothesis

Mice lacking the GPR21 receptor would resist diet-induced obesity and have better glucose tolerance, as an earlier knockout line showed.

What failed

A new GPR21 knockout line made with TALEN gene editing did not keep the better metabolic profile on a normal or high-fat diet.

Broken assumption

The metabolic effect of a knockout mouse comes from the gene that was deleted.

Why

The earlier knockout also disturbed expression of the neighbouring Rabgap1 gene, which may have caused the original effect.

From the published paper: Wang et al. F1000Research, 2016. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

type 2 diabetesGSK-3 betadifferent research area
GSK-3 beta inhibition would restore hepatic insulin sensitivity in diet-induced obese models.
Robust glucose lowering in mouse models did not replicate in a non-human primate crossover study.
Why it matched: mechanism: Metabolic & insulin signalling · failed the same way: Held in the model species, not beyond it

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.