Multiple mouse lines lacking the orphan G protein-coupled receptor, GPR37L1, have elicited disparate cardiovascular phenotypes. The first published Gpr37l1 knockout mice study (1) indicated a marked elevation in systolic blood pressure (SBP; ~60 mmHg), revealing a potential therapeutic opportunity. The phenotype differs from our independently generated knockout line, where male mice exhibited equivalent baseline blood pressure to wildtype (2, 3). Here, we attempted to reproduce the findings of Min et al. (1) by characterizing the cardiovascular phenotype of both the original knockout and transgenic lines alongside a C57BL/6J control line, using the same method of blood pressure measurement. The present study supports the findings from our independently developed Gpr37l1 knockout line (2, 3), namely that SBP and diastolic blood pressure (DBP) are not different in the original Gpr37l1 knockout male mice (SBP: 130.9±5.3 mmHg; DBP: 90.7±3.0 mmHg) compared to C57BL/6J mice (SBP: 123.1±4.1 mmHg; DBP: 87.0±2.7 mmHg) (2, 3). Instead, we attribute the apparent hypertension of the knockout line described by Min et al. (1) to comparison with a seemingly hypotensive transgenic line (SBP 103.7±5.0 mmHg; DBP 71.9±3.7 mmHg). Additionally, we quantified myocardial GPR37L1 transcript in humans, which was suggested to be downregulated in cardiovascular disease (1). We found that GPR37L1 has very low native transcript levels in human myocardium, and that expression is not different in tissue samples from patients with heart failure compared to gender-matched healthy control tissue. These findings indicate that cardiac GPR37L1 expression is unlikely to contribute to the pathophysiology of human heart failure.

中文翻译：

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GPR37L1 参与小鼠血压调节和人类心脏病病理生理学

多个缺乏孤儿 G 蛋白偶联受体 GPR37L1 的小鼠品系引起了不同的心血管表型。首次发表的 Gpr37l1 基因敲除小鼠研究 (1) 表明收缩压 (SBP；~60 mmHg) 显着升高，揭示了潜在的治疗机会。该表型不同于我们独立生成的基因敲除系，其中雄性小鼠表现出与野生型相同的基线血压 (2, 3)。在这里，我们试图重现 Min 等人的发现。(1) 通过使用相同的血压测量方法，在 C57BL/6J 对照品系旁边对原始基因敲除品系和转基因品系的心血管表型进行表征。本研究支持我们独立开发的 Gpr37l1 基因敲除系 (2, 3) 的发现，即原始 Gpr37l1 敲除雄性小鼠（SBP：130.9±5.3 mmHg；DBP：90.7±3.0 mmHg）与 C57BL/6J 小鼠（SBP：123.1±4.1 mmHg；DBP）的 SBP 和舒张压（DBP）没有差异: 87.0±2.7 mmHg) (2, 3)。相反，我们将 Min 等人描述的敲除线的明显高血压归因于。(1) 与看似低血压的转基因品系（SBP 103.7±5.0 mmHg；DBP 71.9±3.7 mmHg）进行比较。此外，我们量化了人类心肌 GPR37L1 转录物，这被认为在心血管疾病中被下调 (1)。我们发现 GPR37L1 在人心肌中具有非常低的天然转录水平，并且与性别匹配的健康对照组织相比，心力衰竭患者的组织样本中的表达没有差异。