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jbm > Volume 28(3); 2021 > Article |
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Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. NRF-2019R1F1A1059208).
Authors’ contributions
Conceptualization: KWB, YKJ, and JIY; Investigation: JSP, JSK, and YSH; Writing-original draft preparation: KWB, YKJ, and SJK; Writing-review and editing: KWB, YKJ, JSP, JSK, YSH, SJK, and JIY; Project administration: JIY; Funding acquisition: JIY; All authors read and approved the final manuscript.
Model | Characteristics | Considerations | ||
---|---|---|---|---|
General | Detailed | |||
SAMP | Average lifespan of less than half of normal mice (SAMP =9.7 months, SAMR=13.3 months);[5] early onset abnormal behavior, skin lesions, cataracts, elevated amyloidosis, and increased spinal lordokyphosis;[5] learning and memory deficits, degenerative joint disease, osteoporosis, tumors, and kidney dysfunction.[7] | Decreased contractility and fiber size, decreased phosphocreatine levels (SAMP8 appeared earlier than SAMP6).[4] | Type II muscle fiber size atrophy is earlier than SAMP6 (this change does not appear in EDL.[13,14] | |
Transmitochondrial mito-miceΔ mtDNA mutator mouse |
Premature aging phenotype, musculoskeletal disorders including sarcopenia.[16] | Muscle-specific mitochondrial aldehyde dehydrogenase 2 activity deficient mice display enhanced oxidative stress in muscle which contributes to muscle atrophy.[17] | Sarcopenia due to age-dependent accumulation of mtDNA mutations.[18] | |
IL-10 KO mouse | Deficiency of IL-10, which regulates the immune response and acts as an anti-inflammatory agent. | Many of the genes differentially expressed from wild-type control mice are associated with mitochondrial metabolism and apoptosis.[19,20] | A good model for linking inflammation and sarcopenia. Differentiation from transmitochondrial mito-miceΔ and mtDNA mutator mice should be considered. | |
Zmpste24−/− mouse | Mimics Hutchinson-Gilford progeria syndrome, stops growing at 5 weeks of age, and has a median survival age of 123 days.[21,22] | Loss of range of motion in the ankle after 5 weeks of age. Neuromuscular performance and selective muscle weakness.[21] | Progeria has many factors that are not suitable for expressing general aging.[23] | |
Ku80+/− mouse Ku80−/− mouse |
Loss of function of Ku80, which aids in repairing DNA double strand breaks and aids in telomere stability.[24] Reduction of type II muscle fiber ratio in soleus muscle (Ku80+/+ > Ku80+/− > Ku80−/−).[25] |
In the presence of normal postnatal growth, it indicates accelerated muscle aging.[24] Exhibits both reduced postnatal growth and severe progeria.[24] |
The difference in the aging phenotype between Ku80+/− and Ku80−/− in the growth process after birth should be considered. | |
Homozygous POLG mutator mice | A homozygous knock-in mouse with impaired DNA polymerase proofreading capability.[27] | Increased mtDNA point mutations and deleted mtDNA. Reduced lifespan (median survival less than 50% of wild-type), kyphosis, osteoporosis, and alopecia. | There is some evidence for a link between mtDNA mutations and increased apoptosis,[28] but evidence for a link to oxidative stress is lacking. | |
ApcMin/+ mouse | It is a model of colon cancer by a mutation in a polyposis coli gene,[29] and cachexia is caused by colon cancer.[30] | After 6 months of age, the weight of the gastrocnemius and soleus muscle decreases by 45% and 23%, respectively, and the average fiber cross section of the soleus muscle decreases by 24%.[31] | The muscle loss occurring in ApcMin/+ appears to be due to the high circulating levels of IL-6.[32] It is necessary to distinguished between cachexia and sarcopenia. | |
MIPKO mouse | An animal lacking muscle-specific inositide phosphatase, an enzyme important for entry, storage, and release of Ca2+ for excitation-contraction coupling in skeletal muscle.[33] | Body weight and muscle mass loss, including reduced EDL fiber cross-sectional area, is apparent by 18 months of age compared to wild-type.[33,34] | Compared to the accelerated aging in other models, the onset of the muscle loss phenotype is relatively late. | |
HSA-MCM mouse | Limb and craniofacial skeletal muscle-specific expression of a human α-skeletal actin protein to occur only upon the administration of a tamoxifen trigger.[35] | In genetically modified mice, incidental events may increase over time, but confusion resulting from this can be minimized. | It should be noted that tamoxifen is drug that can regulate many other hormones in the body. |
SAMP, senescence-prone inbred strains; mtDNA, mitochondrial DNA; IL, interleukin; KO, knock-out; Zmpste24, zinc metallopeptidase STE24; POLG, DNA polymerase γ; ApcMin/+, adenomatous polyposis coli multiple intestinal neoplasia; MIPKO, muscle-specific inositide phosphatase knock-out; HSA-MCM, human skeletal muscle actin Mer-Cre-Mer; SAMR, senescence-resistant inbred strains; EDL, extensor digitorum longus.
Model | Characteristics | Considerations | |
---|---|---|---|
General | Detailed | ||
Akt1−/− mouse Akt2−/− mouse |
Smaller than WT littermates, but overall physiology is minimally altered, including a non-diabetic phenotype.[48] Indistinguishable in appearance at birth from WT mice but develops insulin resistance.[49] |
Both Akt1−/−, Akt2−/− showed lower mass of EDL, gastrocnemius, and quadriceps than WT.[50] | In the case of Akt2−/−, it shows an increase in the mass of the soleus muscle compared to the WT.[50] |
PI3K KO mouse | Several PI3K KO models have exhibited normal growth, except a null model for p85α/p55α/p50α and p85β regulatory subunits that showed a reduced heart size but essentially unchanged skeletal muscle size and morphology.[51] | For, sarcopenia research, it would be good to consider using a null model for the p85α/p55α/p50α and p85β regulatory subunits. | Inhibiting of muscle development factors does not mean inducing muscle loss. Therefore, some of the PI3K mutants are not useful for studying sarcopenia. |
IRS-1 KO mouse IRS-2 KO mouse |
Both IRS-1 and IRS-2 contribute to muscle development, but do not have a specific phenotype for muscle physiology and provide no information on muscle loss. | There are questions about the role of IGF-1 in the area of load-induced muscle hypertrophy.[52-56] Inhibiting of muscle development factors does not mean inducing muscle loss. | |
Mstn−/− mouse | Mstn acts as a regulator of muscle growth via activating and phosphorylating Smad2/3 transcription factors through the Activin IIB membrane receptor.[63-65] | Mstn−/− mice show increased muscle mass[64] and increased expression of anti-apoptotic factors.[69] Increased satellite cell number and type IIb/X fiber cross-sectional area in tibialis anterior muscles.[67] | Mstn−/− mice are more susceptible to atrophy caused by unloading.[70] Aged Mstn−/− mice maintain muscle mass.[72] |
Overexpressing FoxO1 mouse | Weigh less than WT mice and have less relative muscle mass. | Compared to WT mice whose cathepsin L expression is upregulated at 3 months of age, the size of type I and type II muscle fibers is significantly reduced.[82] | The reduction in type I muscle fibers is greater than that of type II muscle fibers.[82] |
mTOR KO mouse | Exhibits reduced weights and cross-sectional area of type II muscles, such as gastrocnemius, tibialis anterior, and plantaris, while both cross-sectional area and weight of soleus were increased (when normalized to body weight) at 6 weeks old.[84] | The morphological changes in muscle-specific mTOR KO mice are particularly pronounced in oxidative fibers, which are similar to muscular dystrophy and myopathy. Therefore, this mutation is sometimes not suitable as a model for sarcopenia study.[84] | |
MuRF1 KO mouse MuRF1/MuRF2 double KO mouse MAFbx KO mouse |
These are mouse transgenic mouse species that do not express well-known proteins related to muscle atrophy. |
Resisted muscle atrophy, showed about a 35% gastrocnemius muscle weight sparing after 14 days of sciatic nerve denervation injury.[85] Skeletal muscle hypertrophy and 38% higher quadriceps muscle weight compared to WT.[86] Resisted muscle atrophy, showed about a 56% gastrocnemius muscle weight sparing after 14 days of sciatic nerve denervation injury.[85] |
Kyung-Wan Baek
https://orcid.org/0000-0002-8445-3773
Youn-Kwan Jung
https://orcid.org/0000-0002-5784-6221
Jin Sung Park
https://orcid.org/0000-0002-6284-9566
Ji-Seok Kim
https://orcid.org/0000-0002-3023-1999
Young-Sool Hah
https://orcid.org/0000-0002-8571-2722
So-Jeong Kim
https://orcid.org/0000-0001-6422-7595
Jun-Il Yoo
https://orcid.org/0000-0002-3575-4123
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