Bcat2-flox Mouse

Bcat2, or Branched-chain amino acid transaminase 2, is a key enzyme in the branched-chain amino acid (BCAA) catabolism pathway. It reversibly catalyzes the initial step of BCAA degradation to branched-chain acyl-CoA, playing a crucial role in maintaining BCAA homeostasis [3]. This metabolic pathway is associated with various biological processes and disease conditions, making Bcat2 an important gene for functional studies, and genetic models like KO/CKO mouse models are valuable tools for exploring its functions.

In pancreatic ductal adenocarcinoma (PDAC), pancreatic tissue-specific knockout of Bcat2 in LSL-KrasG12D/+; Pdx1-Cre (KC) mice impedes the progression of pancreatic intraepithelial neoplasia (PanIN). BCAT2 enhances BCAA uptake to sustain BCAA catabolism and mitochondrial respiration, and its inhibitor ameliorates PanIN formation in KC mice. Also, a lower-BCAA diet impedes PDAC development in mouse models [1].

In melanoma, BCAT2 deficiency leads to impaired tumor cell proliferation, invasion, and migration in vitro, and tumor growth and metastasis in vivo, as it promotes melanoma progression by epigenetically regulating fatty acid synthase (FASN) and ATP-citrate lyase (ACLY) expressions [2].

In colorectal cancer, BCAT2 deficiency promotes tumorigenesis through inhibition of BCAAs metabolism and chronic activation of mTORC1 [6].

In obese with psoriasis mice, the down-regulation of Bcat2 is related to the inhibition of the BCAA catabolism pathway and the aggravation of inflammation [4].

In white adipose tissue (WAT), adipose tissue knockout of Bcat2 in mice increases inguinal WAT browning and thermogenesis, making them resistant to high-fat diet-induced obesity [5].

In conclusion, Bcat2 plays a vital role in BCAA catabolism, and its function is closely related to the development of multiple diseases such as PDAC, melanoma, and colorectal cancer. The use of Bcat2 KO/CKO mouse models has significantly contributed to understanding its role in these disease areas, providing potential therapeutic targets and new insights into disease mechanisms.