Unraveling the pathogenesis of complex cardiovascular diseases, such a
s hypertension, requires the development of in vivo animal model syste
ms. Although large-animal models have long served as the gold standard
, recent advances in transgenic and gene-targeting approaches, mouse g
enetics, and microsurgical technology are initiating a revolution that
has led to the unexpected coupling of in vivo molecular physiology wi
th genetically engineered mice. This article discusses the design of s
trategies to study complex cardiovascular phenotypes in genetically mo
dified mice, including both transgenic and gene-targeted animals. At t
his time, a number of strategies are used to address specific molecula
r or physiological questions, and examples are briefly highlighted. In
addition, a number of potential problems in the generation and use of
transgenic mice in the study of cardiovascular biology are presented.