Studying Metabolic Abnormalities in the Costello Syndrome HRAS G12V Mouse Model: Isolation of Mouse Embryonic Fibroblasts and Their In Vitro Adipocyte Differentiation

Methods Mol Biol. 2021;2262:397-409. doi: 10.1007/978-1-0716-1190-6_24.


Costello syndrome (CS), characterized by a developmental delay and a failure to thrive, is also associated with an impaired lipid and energy metabolism. White adipose tissue is a central sensor of whole-body energy homeostasis, and HRAS hyperactivation may affect adipocyte differentiation and mature adipocyte homeostasis. An extremely useful tool for delineating in vitro intrinsic cellular signaling leading to metabolic alterations during adipogenesis is mouse embryonic fibroblasts, known to differentiate into adipocytes in response to adipogenesis-stimulating factors. Here, we describe in detail the isolation and maintenance of CS HRAS G12V mouse embryonic fibroblasts, their differentiation into adipocytes, and an assessment of adipocyte differentiation.

Keywords: Adipocyte; Costello syndrome; Development; Embryonic; Fibroblast; Metabolism; Mouse model; RASopathy.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Adipogenesis
  • Animals
  • Cell Differentiation*
  • Costello Syndrome / genetics
  • Costello Syndrome / metabolism
  • Costello Syndrome / pathology*
  • Disease Models, Animal*
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Homeostasis
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Knockout
  • Mutation*
  • Proto-Oncogene Proteins p21(ras) / physiology*


  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)