Loss of HCN2 leads to delayed gastrointestinal motility and reduced energy intake in mice

PloS One
Daniel W FisherDane M Chetkovich

Abstract

Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are important regulators of excitability in neural, cardiac, and other pacemaking cells, which are often altered in disease. In mice, loss of HCN2 leads to cardiac dysrhythmias, persistent spike-wave discharges similar to those seen in absence epilepsy, ataxia, tremor, reduced neuropathic and inflammatory pain, antidepressant-like behavior, infertility, and severely restricted growth. While many of these phenotypes have tissue-specific mechanisms, the cause of restricted growth in HCN2 knockout animals remains unknown. Here, we characterize a novel, 3kb insertion mutation of Hcn2 in the Tremor and Reduced Lifespan 2 (TRLS/2J) mouse that leads to complete loss of HCN2 protein, and we show that this mutation causes many phenotypes similar to other mice lacking HCN2 expression. We then demonstrate that while TRLS/2J mice have low blood glucose levels and impaired growth, dysfunction in hormonal secretion from the pancreas, pituitary, and thyroid are unlikely to lead to this phenotype. Instead, we find that homozygous TRLS/2J mice have abnormal gastrointestinal function that is characterized by less food consumption and delayed gastrointestinal transit as compared t...Continue Reading

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Citations

Jun 25, 2019·Frontiers in Molecular Neuroscience·Xiaoli ChangJunxia Xie
Jan 10, 2020·Annual Review of Pharmacology and Toxicology·Bina Santoro, Mala M Shah
May 7, 2021·Nature Communications·Donghai LiuStanley Nattel

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Methods Mentioned

BETA
genotyping
PCR
blood
blood draw
ELISA
transgenic

Software Mentioned

EEGLAB
Sirenia Acquisition
ImageStudio
BLAST
AxioVision
MATLAB

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