Beta-MHC and SMLC1 transgene induction in overloaded skeletal muscle of transgenic mice.
The hypertrophic responses of white fast-twitch muscle to mechanical overload has been investigated using transgenic mice. After 7 wk of overload, endogenous beta-myosin heavy chain (MHC) and slow myosin light chain 1 and 2 (SMLC1, SMLC2) protein were increased in the overloaded plantaris (OP) muscle compared with sham-operated control plantaris (CP)muscle. Concurrently, the levels of endogenous beta-MHC, SMLC1, SMLC2, and cardiac/slow troponin C (CTnC) mRNA transcripts were significantly increased in OP muscles, whereas skeletal troponin C (sTnC) mRNA transcript levels decreased. As an initial attempt to locate DNA sequence(s) that governs beta-MHC induction in response to mechanical overload, multiple independent transgenic lines harboring four different human beta-MHC transgenes (beta 1286, beta 988, beta 450, beta 141) were generated. Except for transgene beta 141, muscle-specific expression and induction (3- to 22-fold) in OP muscles were observed by measuring chloramphenicol acetyltransferase activity (CAT assay). Induction of a SMLC1 transgene (3920SMLC1) in OP muscles was also observed. Collectively, these in vivo data provide evidence that 1) a mechanical overload inducible element(s) is located between nucleotides -450 and +120 of the human beta-MHC transgene, 2) 3,900 bp of 5' sequence is sufficient to confer mechanical overload induction of a SMLC1 transgene, and 3) the increased expression of slow/type I isomyosin (beta-MHC, SMLC1, SMLC2) in response to mechanical overload is regulated, in part, transcriptionally.
Wiedenman
J L
JL
University of Illinois, Urbana-Champaign 61801, USA.
Rivera-Rivera
I
I
Vyas
D
D
Tsika
G
G
Gao
L
L
Sheriff-Carter
K
K
Wang
X
X
Kwan
L Y
LY
Tsika
R W
RW
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D003285:Contractile Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007536:Isomerism; D051379:Mice; D008822:Mice, Transgenic; D015335:Molecular Probes; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D018994:Myosin Light Chains / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D019076:Transgenes
D003285:Contractile Proteins; D015335:Molecular Probes; D018994:Myosin Light Chains; D012333:RNA, Messenger; D018995:Myosin Heavy Chains