Callipyge sheep have muscle hypertrophy in their loin and pelvic limbs due to a mutation in the DLK1-DIO3 imprinted gene cluster, which results in a 30–40% increase in muscle mass without altering live weight. There is also a change in the myosin gene expression causing an increase in fast twitch glycolytic fibers. Previous gene expression studies have shown that DNTTIP1 (terminal deoxynucleotidyl transferase interacting protein 1) is up-regulated in the callipyge muscle. DNTTIP1 is a transcription factor, meaning it binds to a specific DNA sequence to control the amount of mRNA produced. DNTTIP1 may regulate other genes, ultimately leading to muscle hypertrophy. The objectives of this project were to (1) confirm the cellular localization of DNTTIP1 and (2) determine if DLK1 and DNTTIP1 expression can alter myosin promoter activity. Immunohistological detection of DNTTIP1 in transfected C2C12 cells confirmed its nuclear localization. The effect of DLK1 and DNTTIP1 on myosin promoter activity in mouse primary myotubes was tested using luciferase reporter assays. Overexpression of DLK1 and DNTTIP1 were shown to significantly increaseMYH4 (fast twitch glycolytic) promoter activity and decrease MYH7 (slow twitch oxidative) promoter activity. These results were consistent with changes in myosin gene expression in callipyge muscle, indicating that DNTTIP1 has a role in regulating callipyge-induced muscle hypertrophy.
"Determining the Role of DNTTIP1: Piecing Together the Callipyge Sheep Muscle Hypertrophy Pathway,"
The Journal of Purdue Undergraduate Research:
Vol. 4, Article 4.