Mhc¹⁰ homozygotes bearing two copies of Mhc^S531P exhibit a progressive decline in flight ability. Indirect flight muscle (IFM) fibers show reduced power output (with lower work production and slow kinetics); actively beating IFMs exhibit decreased lattice spacing and decreased active number of cross-bridges.

Mhc¹⁰ homozygotes bearing one copy of Mhc^S531P exhibit increased diastolic diameter in aged adults (3 weeks-old) but not in young adults (4 days-old).

Indirect flight muscles of Mhc^DA2B/Mhc^DA2B, Mhc¹⁰/Mhc¹⁰ organisms fail to assemble properly and worsen with age: In late-stage pupae, there are poorly formed myofibrils with abnormal filament packing, and M- and Z-lines are extremely distorted. In 2h-old adults, there are severe defects in packing and alignment of filaments, with remnants of M- and Z-lines diffused throughout the sarcomere. In 2-days old adults, thick and thin filaments are dispersed randomly throughout the myofibril.

Indirect flight muscles of Mhc^DA2B/+, Mhc¹⁰/+ organisms show abnormal myofibril morphology: In late-stage pupae there are small myofibrils that show some filament packing disruptions, and poorly-formed M- and Z-lines. In 2h-old adults, myofibrils show further disruption in thick and thin filament packing and M- and Z-lines are aberrant or absent. In 2d-old adults some myofibrils appear fused, with poorly ordered thick and thin filament arrays, and Z-lines are more closely spaced.

Indirect flight muscles of Mhc^DA1/Mhc^DA1, Mhc¹⁰/Mhc¹⁰ organisms fail to assemble properly and worsen with age: In late-stage pupae, myofibrils are distorted with some disruptions of thick and thin filament packing, M- lines are poorly formed and Z-lines are diffuse. In 2h-old adults, more severe filament irregularities are present, with gaps between thick and thin filaments, aberrant filament alignment. In 2d old adults, adjacent myofibrils tend to merge.

Indirect flight muscles of 2h and 2d old Mhc^DA1/+, Mhc¹⁰/+ show essentially normal myofibrils with occasional filaments missing from myofibrils that display similar to control M- and Z-lines. These muscles show decreased power output, slower kinetics and enhanced stiffness compared to controls.

The overall morphology of DLM fibers in Mhc^R249Q/Mhc^R249Q, Mhc¹⁰/Mhc¹⁰ and Mhc^R249Q/+, Mhc¹⁰/Mhc¹⁰ adults is comparable to controls. At the ultrastructure level, Mhc^R249Q/Mhc^R249Q, Mhc¹⁰/Mhc¹⁰ individuals show no defects in late pupae and in 2h-old adults, but 2 days-old adults show minor degradation of the hexagonal packing around the fibre edges and 7 days-old adults show severe fiber disruption; Mhc^R249Q/+, Mhc¹⁰/Mhc¹⁰ individuals show no obvious defects.

In both Mhc^R249Q/Mhc^R249Q, Mhc¹⁰/Mhc¹⁰ and Mhc^R249Q/+, Mhc¹⁰/Mhc¹⁰ adults, these indirect flight muscles have altered kinetics, including significant decreases in active tension, power generation and net work, but unaltered passive tension, as compared to controls. Mhc^R249Q/Mhc^R249Q, Mhc¹⁰/Mhc¹⁰ adults, but not Mhc^R249Q/+, Mhc¹⁰/Mhc¹⁰ adults show significantly altered cross-bridge kinetics, including decreased maximum frequency of muscle length oscillation, increased 2πc and decreased 2πb.

Mhc^R249Q/+, Mhc¹⁰/Mhc¹⁰ individuals do nor show any obvious defects in DLM fibers.

Both Mhc^+t24.1 hetero- and homo-zygosity in a Mhc¹⁰ background is viable and adults can fly. In the Mhc^+t24.1, Mhc¹⁰ double homozygosity condition, pupal and adult indirect flight muscles show regularly packed myofibrils, with six thin filaments around each thick filament and well-formed sarcomeres.

Mhc^T178I or Mhc^Y583S homozygosity in a Mhc¹⁰ background induces flightless phenotypes and adults typically display a wings-up phenotype; the heterozygosity conditions also lead to significant and progressive decreases in flight ability.

In the Mhc^Y583S, Mhc¹⁰ double homozygosity condition, pupal and 2h-old adult indirect flight muscles show regularly packed myofibrils, with six thin filaments around each thick filament and well-formed sarcomeres; however, 2 days-old adult indirect flight muscles show some disruption in myofibril morphology (thick and thin filaments disperse into neighboring myofibrils), and 7 days-old adult indirect flight muscles show continued filament dispersion (some fusion of neighboring myofibrils). In the Mhc^Y583S/+, Mhc¹⁰/Mhc¹⁰ condition, the pupal and 2h-old adult indirect flight muscles show no obvious defects; however, 2 days-old adult indirect flight muscles show some disruption in myofibril morphology (thick and thin filaments beginning to disperse from myofibrils and possibly fusing with neighboring myofibrils); 7 days-old adult indirect flight muscles show thick and thin filaments merging into neighboring myofibrils.

In the Mhc^T178I, Mhc¹⁰ double homozygosity condition, pupal indirect flight muscles show assembly defects with disrupted myofibril morphology (myofilament subdomains with myofibrils that are poorly aligned with each other and fraying of filaments); 2h-old adult indirect flight muscles show extreme disruption in morphology (thick filaments dispersed in myofibril remnants and reduction in regular sarcomere patterns); 2 days-old adult indirect flight muscles show continued disruption in myofibril morphology (no regular sarcomeric structures and Z-band material scattered throughout the myofibril remnants). In the Mhc^T178I/+, Mhc¹⁰/Mhc¹⁰ condition, the pupal and 2h-old adult indirect flight muscles show no obvious defects; however, 2 days-old adult indirect flight muscles show some disruption in myofibril morphology (myofilaments are missing from the lattice and the sarcomere structural elements are disrupted); in 7 days-old adults there is a severe muscle degeneration.

Both Mhc^R672C hetero- and homo-zygosity in a Mhc¹⁰ background leads to a fully flightless phenotype; the Mhc^R672C homozygosity condition also typically leads to a wings-up phenotype.

In the Mhc^R672C, Mhc¹⁰ double homozygosity condition, pupal indirect flight muscles display severe assembly defects (abnormally shaped and sized myofibrils, and aberrantly localized Z-band material, with poor myofilament organization); 2h-old adult indirect flight muscles show extreme disruption in morphology (thick filaments dispersed in myofibril remnants and reduction in regular sarcomere patterns); these defects become more severe during adulthood. In the Mhc^R672C/+, Mhc¹⁰/Mhc¹⁰ condition, pupal indirect flight muscles show no obvious defects; however, 2h-old adult indirect flight muscles present myofibrils with disrupted myofilament arrays and branching sarcomeres with wavy Z- and M-line material; 2 days-old adult indirect flight muscles show disrupted myofibril morphology with scattered Z-band material, and sarcomeres are further disordered; in 7 days-old adults there is a severe muscle degeneration.

Mhc^K1728del/Mhc¹⁰ transheterozygous adults show significantly decreased jump and climbing abilities, display wing posture defects and fail to beat their wings, indicating a complete lack of flight ability; these are associated with severe sarcomere organization defects and atrophy of the indirect flight muscles.

Indirect flight muscles in Mhc¹⁰/Mhc¹⁰, Mhc^R146N/Mhc^R146N females show normal sarcomere organization at late pupal stage and in 2h-old adults, minor disruptions of thick and thin filament packing in 2-days old adults, and disorder in myofibril morphology in 7-days old adults, including gaps in the hexagonal packing of thick and thin filaments and disruption in the Z- and M-lines, as compared to controls. These muscles also show significantly decreased power generation and work, significantly increased active tension, but do not show a significant change in passive tension, as compared to controls; under optimal power producing conditions, there are further significant decreases in power generation and net work, which is likely due to decreased work generated:work absorbed ratio, as well as in relative muscle length amplitude, as compared to controls. These muscle defects are associated with a progressive decrease in flight index and a lower wing beat frequency, as compared to controls. Mhc¹⁰/Mhc¹⁰, Mhc^R146N/+ individuals display similar, albeit more modest, flight ability defects and indirect flight muscle morphology and performance defects.

The hearts of Mhc¹⁰/Mhc¹⁰, Mhc^R146N/+ individuals display significant decreases in cardiac dimensions (diastolic and systolic diameters) and in fractional shortening, and a significant increase in systolic interval, but do change in heart period, as compared to controls; the heart has an essentially normal myofibrillar integrity and organization in 1-week old adults, but displays myofibrillar discontinuities in 3-weeks old adults, as compared to controls; cardiomyocyte thickness in both young and aged mutant adults shows no statistically significant differences, as compared to controls.

Adults bearing two copies of either Mhc^R1845W, Mhc^E1883K or Mhc^E1883K in an Mhc¹⁰ homozygous background present a wings-up phenotype, are virtually flightless, jump significantly shorter distances, and the indirect flight muscles exhibit severe disruptions in muscle fibers, including torn fibers that are bunched at the attachment sites, disrupted sarcomere integrity and accumulation of myosin and poly-ubiquitin aggregates, as compared to controls. At the ultrastructural level, the indirect flight muscles of pupae and young adults lack the normal round morphology, lack the regular sarcomeric arrangement and show misaligned subsections of myofibrils, with several areas showing disruption of the hexagonal arrangement of thick and thin filaments, as compared to controls; these defects are more severe in young adults compared to pupae.

Flies expressing Mhc^P838L/Mhc^P838L in a Mhc¹⁰/Mhc¹⁰ background, exhibit impaired flight ability. The indirect flight muscles in 2 day old flies display largely normal myofibril morphology and sarcomeric structure, but a few show occasional minor abnormalities in Z-disk regularity. At 3 weeks post-eclosion, indirect flight muscles show areas with Z-band irregularities, sarcomere gaps, abnormalities in myofibrillar shape and orientation, and defects in myofilament packing, as compared with controls. 2-3 day old flies expressing Mhc^P838L/Mhc^P838L in a Mhc¹⁰/Mhc¹⁰ background show no significant difference in indirect flight muscle power, wing beat frequency, active stiffness, isometric tension or rigor stiffness as compared with controls (Mhc^+t12.4/Mhc^+t12.4 in a Mhc¹⁰/Mhc¹⁰ background).

Female flies expressing Mhc^E701K in a homozygous Mhc¹⁰ background completely lack flight ability. Two day old flies are unable to beat their wings, and a "wings-up" phenotype is present. The jump ability of two day old females is also severely reduced compared with controls.

Myosin isolated from the indirect flight muscles of flies expressing Mhc^E701K in a homozygous Mhc¹⁰ background has significantly reduced catalytic activity compared to control myosin. CaATPase, MgATPase, and actin-stimulated MgATPase activity (V[[max]]) and catalytic efficiency (the ratio of V[[max]] / actin affinity relative to ATPase (K[[m]]) ) are all reduced. K[[m]] is increased. The actin sliding velocity stimulated by mutant myosin is significantly reduced compared to that of control myosin.

Myosin isolated from the indirect flight muscles of flies expressing Mhc^E701K in a Mhc¹⁰ mutant background has an increased propensity to aggregate compared to control myosin. The mutant myosin molecules have collapsed heads that frequently pack into aggregated clumps reminiscent of wild-type motors exposed to elevated temperatures. Only 22.5% of myosin exhibit the normal two headed structure.

The indirect flight muscles of female flies expressing Mhc^E701K in a Mhc¹⁰ mutant background exhibit ultrastructural defects that become progressively worse with age. During the late pupal stages M-lines and Z-discs are distinguishable, but the myofibrils show disruption of integrity and lack the round shape seen in controls. In two hour old flies the myofibrils show loss of visible M-lines, with decreases in myofibril integrity and hexagonal packing. By two days old the myofibrils show severe ultrastructural deterioration, with broken and streaming Z-discs and a loss of thick filaments and M-lines. The fibers show sarcolemmal membrane invaginations and protrusions and contain rimmed vacuoles fused with additional membranes. Cyclical spiral membranes are seen that are reminiscent of the sarcolemmal inclusions found in human skeletal myopathy.

The flight ability of Mhc¹⁰ mutants expressing Mhc^IFI-9b is normal.

Adults expressing Mhc^IFI-9b in a Mhc¹⁰ mutant background show normal jumping ability.

Flies expressing Mhc^EMB-9a in a Mhc¹⁰ mutant background are flightless.

The jump ability of flies expressing Mhc^EMB-9a in a Mhc¹⁰ mutant background appears impaired.

Compared with wild-type, the flight ability of Mhc¹⁰ mutants expressing Mhc^15b is impaired. The flight ability of these flies declines more rapidly with age than that of controls.

Compared with controls, Mhc¹⁰ mutant flies expressing Mhc^15b display a reduced ability to jump.

Electrophysiological responses of flight muscles in Mhc¹⁰ mutants expressing Mhc^15b appear normal.

Myofibrils of Mhc¹⁰ mutant flies expressing Mhc^IFI-7a show no differences in assembly or stability when compared to controls.

Mhc¹⁰ mutant flies expressing Mhc^IFI-7a exhibit no impairment in flight or jump ability compared to controls.

Expression of Mhc^EMB-7d in Mhc¹⁰ mutants allows normal myofibrillar assembly evidenced at 2 hours post-eclosion. By two days indirect flight muscle myofilaments do show some disruption.

Transgenic Mhc¹⁰ mutant flies expressing Mhc^EMB-7d show impairment in jump ability and they are not able to fly.

52% of homozygous adults have an upheld wing phenotype, 42% have their wings held down and 6% hold their wings in the normal position. The indirect flight muscle fibres appear normal. 4% of heterozygotes have an upheld wing phenotype. The indirect flight muscle fibres appear normal. 44% of Mhc¹⁰/+ ; Mhc^{R57-24.Act88F}/+ flies have their wings held down and 56% hold their wings in the normal position. The indirect flight muscle fibres appear normal. 76% of Mhc¹⁰/Mhc¹³ adults have an upheld wing phenotype, 24% have their wings held down and 0% hold their wings in the normal position. 39% of the indirect flight muscle fibres of mutant adults are hypercontracted, 61% show a partial hypercontraction phenotype.

The myofibrillar ultrastructure in the indirect flight muscle of animals carrying Mhc^EMB-3b in a Mhc¹⁰ background is identical to wild type at the pupal stage. However, 2 days after eclosion, the filament packing is disrupted, and the normal rigid hexagonal arrangement of thick and thin filaments is disturbed. The myofibrils appear cracked and frayed when viewed longitudinally, because of gaps between thick and thin filaments and/or loss of thick and thin filaments. The phenotype becomes progressively worse with age. The myofibrillar ultrastructure in the indirect flight muscle of animals carrying Mhc^IFI-3a in a Mhc¹⁰ background is identical to wild type at the pupal stage. The myofilaments remain highly ordered and identical to wild type for at least two weeks following eclosion. Animals carrying Mhc^+memb in a Mhc¹⁰ background show severe cracking and fraying of myofibrils in the indirect flight muscle. The basic sarcomere pattern is disrupted at 2 days after eclosion and 2 weeks after eclosion, myofibrils are no longer discernible.

Indirect flight muscle (IFM) myofibrils expressing Mhc^+memb in a Mhc¹⁰ background show ultrastructural deterioration, which begins soon after the age at which Drosophila normally begin using the IFMs. These flies cannot beat their wings. These flies can jump, but achieve much shorter differences than wild-type flies. Two day old flies expressing Mhc^EMB-IC in a Mhc¹⁰ background show some ultrastructural deterioration of the indirect flight muscle myofibrils. These flies cannot beat their wings. These flies can jump, but achieve much shorter differences than wild-type flies. Two day old flies expressing Mhc^IFI-EC in a Mhc¹⁰ background have indirect flight muscle myofibrils which are almost indistinguishable from wild type. These animals can fly.

Flies carrying Mhc^emb.ex18 in a Mhc¹⁰ mutant background exhibit normal-looking myofibrils at the pupal stage in the central regions, but myofilaments at the periphery are less organized. In young adults, the myofibrils are disorganised with cracking and fraying throughout. In 1-week old flies the myofibrils appear fairly well organised. The appear compacted and smaller in diameter, but there is no cracking or fraying at the periphery.

Flies carrying Mhc^+memb in a Mhc¹⁰ mutant background exhibit normal-looking myofibrils at the pupal stage. In young adults, the myofibrils are disorganised with cracking and fraying throughout. In 1-week old flies, the myofibrils are completely disorganised.

Arrays of thin filaments and malformed Z-discs accumulate in the indirect flight muscles (IFMs) of Mhc¹⁰ flies, however, thick filaments are absent. Mhc¹⁰ flies expressing Mhc^{R57-24.Act88F} have thick filaments that are associated with myofibril-like structures in the IFMs. These myofibrils have Z-discs and occasional M-lines, however, sarcomere length and the length of the thick filaments is variable. The Z-discs are thicker than wild type. Many of the thick filaments are packed in a hexagonal manner and are frequently interdigitated with thin filaments. Often, six thin filaments surround each thick filament, as in wild type. However, the myofibrils are rarely circular in cross-section and show a variability in size compared to wild type. Mhc¹⁰ flies expressing Mhc^R21-1.Act88F have hollow thick filaments and myofibril-like structures in the IFMs. Hexagonal packing of the thick filaments with arrays of six thin filaments surrounding each thick filament is seen, as in wild type. Less rescue is seen than with Mhc^{R57-24.Act88F}.

Homozygotes are flightless, one copy of Mhc^+t41.9 improves flying ability but not to wild type levels. Homozygotes are also unable to jump, one copy of Mhc^+t41.9 improves jumping ability.

Mhc RNA, protein and thick filaments do not accumulate in the indirect flight muscles and jump muscles of the adult, and levels are reduced in the leg muscles.

Indirect flight muscles accumulate little or no MHC, have no thick filaments, and show no organized myofibrils. All 32 TDT cells lack thick filaments and lack myofibril organization. Flies cannot jump. Leg muscles accumulate 55% normal amounts of MHC (O'Donnell, Collier, Mogami and Bernstein, 1989). homozygous viable

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor of visible phenotype of up¹

Mhc[+]/Mhc¹⁰ is a suppressor of visible phenotype of wupA^hdp-2

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of visible phenotype of wupA^hdp-2

Mhc¹⁰ is a non-suppressor of flightless | heat sensitive phenotype of Act57B^M306L.UAS, Scer\GAL4^Act88F.PB

Mhc[+]/Mhc¹⁰ is a non-suppressor of visible phenotype of up¹⁰¹

Mhc[+]/Mhc¹⁰ is a non-suppressor of flightless phenotype of up¹⁰¹

Mhc[+]/Mhc¹⁰ is a non-suppressor of flightless phenotype of wupA^hdp-2

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a non-suppressor of flightless phenotype of wupA^hdp-2

Mhc^K1728del/Mhc¹⁰ has indirect flight muscle cell | adult stage phenotype, non-suppressible by tn^UAS.cDa/Scer\GAL4^Mef2.PR

Mhc^K1728del/Mhc¹⁰ has sarcomere | adult stage phenotype, non-suppressible by tn^UAS.cDa/Scer\GAL4^Mef2.PR

Mhc¹⁰ is a suppressor of indirect flight muscle | adult stage phenotype of tono¹

Mhc¹⁰ is a suppressor of indirect flight muscle | adult stage phenotype of tono²

Mhc¹⁰ is a suppressor of dorsal longitudinal indirect flight muscle cell | heat sensitive phenotype of Act57B^M306L.UAS, Scer\GAL4^Act88F.PB

Mhc¹⁰ is a suppressor of indirect flight muscle cell phenotype of Scer\GAL4^Mef2.PR, bru1^GD8699

Mhc[+]/Mhc¹⁰ is a suppressor | partially of indirect flight muscle cell phenotype of Act57B^K328Q.UAS, Scer\GAL4^Mef2.PR

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of indirect flight muscle cell phenotype of up¹

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of myosin filament & indirect flight muscle phenotype of up¹

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of striated muscle thin filament & indirect flight muscle phenotype of up¹

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of Z disc & indirect flight muscle phenotype of up¹

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor of wing phenotype of up¹

Mhc[+]/Mhc¹⁰ is a suppressor of indirect flight muscle cell phenotype of wupA^hdp-2

Mhc[+]/Mhc¹⁰ is a suppressor of wing phenotype of wupA^hdp-2

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of indirect flight muscle cell phenotype of wupA^hdp-2

Mhc^{R57-24.Act88F}/Mhc¹⁰ is a suppressor | partially of wing phenotype of wupA^hdp-2