Ghr-KO Mouse

Ghr, the growth hormone receptor, is a membrane-bound receptor belonging to the class I cytokine receptor superfamily. Growth hormone (GH) binding to Ghr induces cell differentiation, maturation, anabolism, and proliferation. The GH-GHR-IGF1 axis activates the JAK2/STAT5 pathway to stimulate IGF1 synthesis, playing significant roles in somatic growth, such as cell proliferation, differentiation, division, and survival [2,3]. Genetic models, like gene knockout mice, are valuable for studying Ghr's functions.

In GHR-/-mice, there are decreased body weights but obesity. Despite obesity, these mice seem protected from age-related white adipose tissue inflammation and immune cell infiltration, with modest and depot-specific changes to immune cell populations in white adipose tissue (WAT) depots [4]. In another study, knockdown of GHR in HCC cells enhanced their sensitivity to sorafenib, potentially via inhibiting the PI3K/AKT/ERK1/2 signaling pathway [1]. Also, GHR deficiency in gastric cancer cells inhibited cell growth and induced apoptosis, arresting cells in the G1 phase, and was associated with inactivation of the PI3K/AKT signaling pathway [2].

In conclusion, Ghr is essential for mediating the effects of growth hormone, influencing multiple biological processes including cell growth, metabolism, and immune cell regulation in adipose tissue. Gene knockout models of Ghr have provided insights into its role in diseases such as cancer and obesity-related inflammation, contributing to our understanding of disease mechanisms and potentially guiding future therapeutic strategies.