Sequencing, expression analysis, and mapping of three unique human tropomodulin genes and their mouse orthologs.
Tropomodulin (TMOD) is the actin-capping protein for the slow-growing end of filamentous actin, and a neuronal-specific isoform, neuronal tropomodulin (NTMOD), is the major binding protein to brain tropomyosin in rat. The Drosophila TMOD homolog, Sanpodo, alters sibling cell fate determination, so we used a cross-species approach to identify additional TMOD family members that may play a critical role in this process. We characterized the human and mouse orthologs to rat NTMOD (TMOD2 and Tmod2, respectively) as well as two novel tropomodulin family members (TMOD3, Tmod3 and TMOD4, Tmod4). Their expression patterns vary extensively, from ubiquitous (TMOD3 and Tmod3) to muscle (TMOD4) or neuronal tissues only (TMOD2 and Tmod2). TMOD2 and TMOD3 map next to one another on chromosome 15q21.1-q21.2, and their mouse orthologs map to a homologous region on mouse chromosome 9; TMOD4 maps to the telomeric end of 1q12 and Tmod4 to a homologous region of mouse chromosome 3. Their location and expression patterns make TMOD2 and TMOD3 candidate genes for amyotrophic lateral sclerosis 5 (ALS5) and dyslexia-1 (DYX1) and TMOD4 a candidate gene for limb girdle muscular dystrophy 1B (LGMD1B). Our mapping efforts revealed new regions of paralogy among chromosomes 1q, 9q, 15q, and 19p.
Cox
P R
PR
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Zoghbi
H Y
HY
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002884:Chromosomes, Human, Pair 15; D002888:Chromosomes, Human, Pair 19; D002899:Chromosomes, Human, Pair 9; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D051348:Tropomodulin
D002352:Carrier Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C495829:TMOD1 protein, human; C495833:TMOD2 protein, human; C495836:TMOD3 protein, human; C495839:TMOD4 protein, human; C495831:Tmod1 protein, mouse; C495832:Tmod1 protein, rat; C495834:Tmod2 protein, mouse; C495837:Tmod3 protein, mouse; C495838:Tmod3 protein, rat; C495840:Tmod4 protein, mouse; C495841:Tmod4 protein, rat; D051348:Tropomodulin