Igfbp4-flox Mouse

Igfbp4, Insulin-like growth factor binding protein 4, is highly expressed in adipocytes and osteoblasts. It is an inhibitor of IGFs in vitro and is involved in the regulation of IGF-I signaling pathway, which has wide-ranging effects on cell growth, differentiation, and metabolism [3].

In Igfbp4 null mice (Igfbp4-/-), inguinal and gonadal white adipose tissue had decreased weights and Pparγ expression. Cultures of primary bone marrow stromal cells and ear mesenchymal stem cells from these mutant mice showed reduced adipogenesis. Also, there were sexual differences in adipocyte expansion on a high-fat diet, indicating that Igfbp4 is required for inguinal fat expansion in female mice but not in male mice [3]. In addition, in type 2 diabetes (T2D) patients, higher levels of total and intact IGFBP4 were associated with all-cause mortality, suggesting its role in T2D-related mortality [1]. In chronic lymphocytic leukemia (CLL), IGFBP4 was identified as an independent prognostic factor, where high IGFBP4 risk scores were associated with a high incidence of trisomy 12q [2].

In conclusion, Igfbp4 plays essential roles in adipogenesis and the distribution of adipose depots, as revealed by Igfbp4-/-mouse models. It also has implications in diseases such as T2D and CLL, highlighting its significance in understanding the pathophysiology of these conditions.