Publications by authors named "Deon Smith"

The kinase suppressor of ras 2 (KSR2) gene resides at human chromosome 12q24, a region linked to obesity and type 2 diabetes (T2D). While knocking out and phenotypically screening mouse orthologs of thousands of druggable human genes, we found KSR2 knockout (KSR2(-/-)) mice to be more obese and glucose intolerant than melanocortin 4 receptor(-/-) (MC4R(-/-)) mice. The obesity and T2D of KSR2(-/-) mice resulted from hyperphagia which was unresponsive to leptin and did not originate downstream of MC4R.

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Article Synopsis
  • Researchers created a high-throughput method to knockout mouse versions of potential drug targets in the human genome to study body fat regulation.
  • They used dual-energy X-ray absorptiometry (DXA) technology to measure body fat in knockout (KO) and wild-type (WT) mice, finding that their data showed a normal distribution.
  • The study identified specific KO lines associated with lean and obese phenotypes, confirming their findings with additional cohorts, and demonstrating that the screening method can effectively identify important genes involved in body fat regulation.
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