Generation and identification of endothelial-specific Hrh2 knockout mice

Area of Science:

• Cardiovascular and cerebrovascular research
• Pharmacology
• Genetics and genomics

Background:

• Histamine H2 receptor (HRH2) is implicated in cardiovascular and cerebrovascular diseases.
• Previous Hrh2 knockout mice did not fully represent HRH2's function in specific cell types.
• Understanding endothelial HRH2 is crucial for disease research.

Purpose of the Study:

• To create novel mouse models for studying endothelial HRH2.
• To investigate the physiological and pathophysiological roles of endothelial HRH2.
• To facilitate research into HRH2's involvement in disease development and treatment.

Main Methods:

• Constructed a targeting vector with loxp sites flanking Hrh2 exon 2 and a neomycin resistance gene.
• Electroporated the vector into C57BL/6J embryonic stem cells.
• Generated Hrh2flox/+ mice and subsequently endothelial cell-specific knockout (ECKO) mice using Cdh5-Cre.
• Confirmed Hrh2 deletion specifically in endothelial cells.

Main Results:

• Successfully generated Hrh2flox/+ and Hrh2ECKO mice.
• Hrh2 deletion was confirmed exclusively in endothelial cells of ECKO mice.
• Both Hrh2flox/+ and Hrh2ECKO mice exhibited normal health, fertility, and no apparent abnormalities.

Conclusions:

• Novel Hrh2flox/+ and Hrh2ECKO mouse models have been successfully created.
• These models provide a valuable tool for dissecting the specific functions of endothelial HRH2.
• The models offer new avenues for exploring HRH2's role in cardiovascular and cerebrovascular diseases and potential treatments.