Table 1.

Tmod and Lmod Isoform Expression, Localizations, and Functions in Vertebrate Muscles

Proteina	Tissue and Cell Expression	Developmental Expression in Mouse and Human	Cytoskeletal Localizations	Mouse Phenotype or Human Disease due to Loss of Tmod or Lmod	References
Tmod1b	cardiac muscle	E8.0 to adult	thin filament pointed ends in sarcomeres	mouse embryonic lethal E8.5–9.5; failure of embryonic cardiac myofibril assembly and contractility; aborted cardiac development; longer thin filaments after acute depletion or inhibition in cardiac myocytes	8, 9, 29, 30, 75
	skeletal muscle	E9.5 to adult	thin filament pointed ends in sarcomeres; sarcoplasmic reticulum (SR) or T-tubule-associated compartment; costameres at sarcolemma	mouse skeletal muscle weakness; normal thin filament lengths due to compensation by Tmod3 and Tmod4; perturbed SR organization and Ca2+-handling due to Tmod3 relocation to thin filament pointed ends; longer thin filaments after acute depletion in adult skeletal muscle	7, 8, 29, 63
	smooth muscle	unknown	F-actin-associated puncta throughout cells	unknown	26
Tmod3c	skeletal muscle	unknown	SR-associated actin cytoskeleton	mouse embryonic lethal E15.5–18.5	8, 9, 109, 110
Tmod4	skeletal muscle	unknown, to adult	thin filament pointed ends in sarcomeres	mouse skeletal muscle normal due to compensation by Tmod1	8, 9, 22, 63
Lmod1d	cardiac muscle (embryonic)	E9.5–12.5	unknown	unknown	27
	Smooth muscle (vascular and visceral)	E13.5 to adult	diffuse staining in F-actin-rich regions between dense bodies	human and mouse postnatal or juvenile lethality due to MMIHS; aberrant actin filament assembly in bladder and intestinal smooth muscle and defective contractility	21, 25, 26, 27
	extraocular and sternothyroid striated muscle	unknown	A-band in sarcomeres	unknown	25, 28
Lmod2	cardiac muscle	mouse: E8.5 to adult human: fetal heart, adult	thin filaments, near pointed ends and along the length of thin filaments in sarcomeres; A-band in sarcomeres	mouse juvenile lethality due to dilated cardiomyopathy, with shorter thin filaments and reduced contractile force in cardiomyocytes	3, 7, 11, 12, 25, 27, 40
	skeletal muscle	E9.5 to adult	unknown	no apparent phenotype	7, 11, 27, 63
Lmod3	cardiac muscle	E12.5 to adult	unknown	mouse smaller heart; modestly impaired function	13, 16, 27
	skeletal muscle	mouse: E10.5 to adult human: 14 weeks gestation to adult	thin filaments, near pointed ends and along the length of thin filaments in sarcomeres; A-band in sarcomeres	Human and mouse neonatal lethality due to severe muscle weakness and respiratory insufficiency; nemaline myopathy, with shorter thin filaments and actin filament accumulation in nemaline bodies; fast fiber atrophy in mice	13, 14, 16, 17, 27, 63

^aTmod2 is not included as it is only expressed in neurons (9, 23). For simplicity, Tmod data on chicken and frog are not included.

^bTmod1 is also expressed in nonmuscle cells, such as red blood cells and lens fiber cells (9).

^cTmod3 is expressed ubiquitously, and is the sole Tmod in endothelial cells, polarized epithelial cells, megakaryocytes, and platelets (9, 110).

^dLmod1 is also expressed in neurons of the central nervous system, including the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons (19), as well as some endocrine glands (20). See also the Human Protein Atlas, http://www.proteinatlas.org/.