Developmental changes in rat cardiac titin/connectin: transitions in normal animals and in mutants with a delayed pattern of isoform transition.
Rat cardiac titin undergoes developmental changes in isoform expression during the period from late embryonic through the first 20-25 days of life. At least five size classes of titin isoforms have been identified using SDS agarose gel electrophoresis. The longest normal isoform is expressed in the embryonic stages, and it is progressively replaced with increasingly smaller versions. The isoform switching is consistent with changes in resting tension from lower values in one-day neonates to higher levels in adult myocytes. Considerable micro-heterogeneity in alternative splicing patterns also was found, particularly in the N2BA PEVK region of human, rat, and dog ventricle. A rat mutation has been identified in which the embryonic-neonatal titin isoform transitions are markedly delayed. These mutant animals may prove useful for examining the role of titin in stretch-activated signal transduction and in the Frank-Starling relationship.
University of Wisconsin-Madison, Madison, WI 53706, USA. mgreaser@ansci.wisc.edu
Marion L
ML
Greaser
Paul R
PR
Krzesinski
Chad M
CM
Warren
Brian
B
Kirkpatrick
Kenneth S
KS
Campbell
Richard L
RL
Moss
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D064211:Connectin; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D005091:Exons / Q000235:genetics; D005318:Fetal Heart / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006325:Heart Atria / Q000196:embryology / Q000378:metabolism; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000502:physiology
D064211:Connectin; D018076:DNA, Complementary; D009124:Muscle Proteins; D020033:Protein Isoforms; C577285:TTN protein, human; D011494:Protein Kinases