Characterization of Cre recombinase models for the study of adipose tissue

Abstract

The study of adipose tissue in vivo has been significantly advanced through the use of genetic mouse models. While the aP2-CreBI and aP2-CreSalk lines have been widely used to target adipose tissue, the specificity of these lines for adipocytes has recently been questioned. Here we characterize Cre recombinase activity in multiple cell populations of the major adipose tissue depots of these and other Cre lines using the membrane-Tomato/membrane-GFP (mT/mG) dual fluorescent reporter. We find that the aP2-CreBI and aP2-CreSalk lines lack specificity for adipocytes within adipose tissue, and that the aP2-CreBI line does not efficiently target adipocytes in white adipose depots. Alternatively, the Adiponectin-CreERT line shows high efficiency and specificity for adipocytes, while the PdgfRα-CreERUCL and PdgfRα-CreERJHU lines do not efficiently target adipocyte precursor cells in the major adipose depots. Instead, we show that the PdgfRα-Cre line is preferable for studies targeting adipocyte precursor cells in vivo.

Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution

“…In complementary studies, we also examined whether βKlotho is expressed in TECs expressing FoxN1, a transcription factor that is critical for thymopoiesis (26). To do this, we used transgenic mice harboring a fluorescent membrane dTomato/membrane EGFP (mT/mG) Cre reporter construct (27) that marks FoxN1 Cre excision by a heritable switch from membrane-targeted tdTomato expression to membrane-targeted EGFP expression. Examination of Foxn1-Cre:mT/mG mice thymi revealed that βKlotho is colocalized with Foxn1 + TECs (Fig.…”

The dual role of BMP4 in adipogenesis and metabolism

“…However, a recent study suggests that Ap2 is not specific for the adipocytes, but it is highly expressed also in endothelial cells. 41 Indeed, previous transgenic studies based on the Ap2 promoter are now being revisited by the generation of the corresponding Adiponectin promoter-based transgenic model with very different phenotypic outcomes. 42,43 In this respect, the metabolic outcome shown in the work of Qian et al, 23 where an Ap2-Bmp4 mouse model was used needs to be re-evaluated as Bmp4 might be produced in various organs from the endothelial cells, and after secretion regulate the function of cells and tissues in a paracrine and maybe also endocrine manner.…”

Molecular and cellular mechanisms of adipogenesis

“…Недавно было показано, что клетки-предшественники адипоцитов белой жировой ткани экспрессируют PDGFRα (CD140a), который также является маркером всех адипоцитов в белом жире [17]. Имеющаяся линия трансгенных мышей PDGFRα-Cre является одной из наиболее адекватных для исследований клеток-пред-шественников жировой ткани, так как позволяет произ-водить делецию в преадипоцитах [18].…”

“…Это приводит к его активации, осуществляя своеобразную связь между Сахарный диабет. 2015;18(2): [12][13][14][15][16][17][18][19] инсулиновым и цАМФ-зависимым каскадами. Наконец, инсулин приводит к активации гена Srebf1, играющего значительную роль на последующих стадиях адипоге-неза [44].…”

“…2015;18 (2): [12][13][14][15][16][17][18][19] ности, не до конца выяснен механизм формирования многомерных комплексов транскрипционных факто-ров и перестройки хроматина, вызывающие переход от недифференцированного состояния к дифферен-цированному. В настоящем обзоре рассмотрены основные сиг-нальные пути и транскрипционные факторы, представ-ляющие интерес в качестве новых мишеней для поиска лекарственных средств.…”