Table 9.
Tm mouse models generated to study the functional differences among the isoforms
| Gene affected (Tm isoform) | Comment | Reference |
| Tpm1 (Tm3) | Rat Tm3 driven by the human β-actin promoter. The transgene causes alterations in Tm3-associated actin filaments, resulting in dystrophic features in some skeletal muscles and susceptibility to exercise-induced damaged and reduced neurite outgrowth in isolated cultured neurons. |
65, 80, 90, 91 |
| TPM3 (Tm5NM1) | Human Tm5NM1 driven by the human β-actin promoter. the transgene results in alterations in Tm5NM1-associated actin filaments that enhance neurite outgrowth in isolated cultured neurons. |
16, 80, 92 |
| Tpm3 (γTm muscle) | αTmslow driven by the cardiac specific α-myosin heavy chain promoter. No morphological abnormalities in the sarcomeres of the heart. However, physiological assessment of the hearts reveals a hyper dynamic effect on systolic and diastolic performance. |
112 |
| Tpm1 (αTm muscle) | αTmfast driven by the cardiac specific α-myosin heavy chain promoter. The hearts from these mice exhibit no morphological or physiological changes. |
110, 113 |
| Tpm2 (βTm muscle) | βTm driven by the cardiac specific α-myosin heavy chain promoter. No morphological or pathological alterations in cardiac morphology or sarcomeric structures are observed. However, there is an increase in the activation of the thin filament by strongly bound cross-bridges, an increase in the Ca2+ sensitivity and a decrease in the rightward shift of the Ca2+-force relation induced by cAMP-dependent phosphorylation. |
93,114, 115 |
| (Chimericα/βTm-1) | Chimera 1: αfTm:aa 1–257 and βTm: aa 258–284. Substitution of the carboxyl terminal end of αTm for that of βTm. Transgene driven by cardiac specific α-myosin heavy chain promoter. No morphological or pathological changes are observed in the hearts or myofibers. However, hearts exhibit functional alterations in cardiac performance with a decrease in their rates of contraction and relaxation. |
116 |
| (Chimeric α/βTm-3) | Chimera 3: replaces aa 175–190 of αfTm with the corresponding sequence in βTm. Transgene driven by cardiac specific α-myosin heavy chain promoter. No morphological or pathological changes are observed in the hearts. However, there were decreases in the maximum rates of contraction and relaxation. |
117 |
| (Chimeric α/βTm-2) | Chimera 2: replaces aa 175–190 and 258–284 of αfTm with the corresponding sequence in βTm. Transgene driven by cardiac specific α-myosin heavy chain promoter. Hearts exhibit abnormalities in cardiac performance, especially with decreases in their rates of contraction and relaxation. |
118 |
| Tpm3 (Deletion of all cytoskeletal products from the Tpm3 gene) | Targeted deletion of exon 1b from the Tpm3 gene eliminating all cytoskeletal products from this gene. Embryonic lethal. |
87 |
| Tpm3 (deletion of Tm5NM4 and Tm5NM7) | Targeted deletion of exon 9c from the Tpm3 gene eliminating Tm5NM4 and Tm5NM7. Histological examination of the brains from these mice reveals no gross morphological defect. |
119 |
| Tpm3 (deletion of Tm5NM1 and Tm5NM2) | Targeted deletion of exon 9d from the Tpm3 gene eliminating Tm5NM1 and Tm5NM2. Skeletal muscle from these mice have altered excitation-contraction coupling. Small impact on neurite outgrowth in isolated cultured neurons. Primary embryonic fibroblasts have altered motility properties. |
76, 90, 92, 93 |
| Tpm1 (deletion of the muscle αTm isoform from the Tpm1 gene) | Mice die between embryonic day 9.5 and 13.5 | 86 |
| Tpm2 (Deletion of the muscle βTm isoform from the Tpm1 gene) | Embryonic lethal. | 84, Rajan and Wieczorek, unpublished data |