Table 3.

Musculoskeletal disorders associated with genetic intervention of autophagy in mice.

Setting	Genetic intervention	Effects on disease phenotype	Ref.
Bone loss	Chondrocyte‐specific deletion of Atg7	Reduced femoral and tibia lengths, linked to increased ER storage of PC2 and defective secretion of COL2A1, at the postnatal stage	Cinque et al (2015)
Bone loss	Osteoblast‐specific deletion of Atg5	Reduced trabecular bone volume in 9‐month‐old mice, linked to reduced mineralization capacity	Nollet et al (2014)
Bone loss	Conditional osteoblast‐specific deletion of Fip200	Exacerbated osteopenia due to defective osteoblast terminal differentiation	Liu et al (2013a)
Bone loss	Conditional osteoblast progenitor‐specific deletion of Atg7	Reduced bone mass at both developmental and adult age, linked to reduced mineralization capacity and promoted ER stress	Li et al (2018)
Bone loss	Conditional osteocyte‐specific deletion of Atg7	Reduced bone mass in 6‐month‐old mice linked to increased ROS levels and reduced osteoclast number	Onal et al (2013)
Bone loss	Osteoclast‐specific deletion of Atg5	Increase trabecular bone volume and reduced ovariectomy‐induced bone loss	DeSelm et al (2011)
Bone loss	Myeloid cell‐specific deletion of Atg7	Reduced glucocorticoid‐ and ovariectomy‐induced osteoclast differentiation and bone loss	Lin et al (2016)
Exercise intolerance	Whole‐body allelic loss of Becn1	Decreased endurance and altered glucose metabolism during acute exercise, impaired exercise‐stimulated protection against HFD‐induced glucose intolerance	He et al (2012)
Exercise intolerance	Whole‐body knock‐in of mutant Bcl2AAA	Decreased endurance and altered glucose metabolism during acute exercise, impaired exercise‐stimulated protection against HFD‐induced glucose intolerance	He et al (2012)
Muscular dystrophy	Whole‐body deletion of Col6a1	Myopathic defects associated with impaired autophagic flux and aberrant organelle accumulation	Grumati et al (2010) Chrisam et al (2015)
Muscular dystrophy	Muscle‐specific knock‐in of Akt	Exacerbated muscular dystrophy after autophagy inhibition	Grumati et al (2010)
Muscular dystrophy	Whole‐body deletion of Trim32	Exacerbated muscular atrophy associated with impaired autophagic induction	Di Rienzo et al (2019)
Osteoarthritis	Articular cartilage‐specific deletion of FoxO1	Development of osteoarthritis‐like pathologies	Wang et al (2020a)
Osteoporosis	Whole‐body deletion of Optn	Early elevated osteoporotic bone loss, senescence of MSCs, and enhanced adipogenesis	Liu et al (2020c)
PDB	Whole‐body deletion of Optn	Bone lesions similar to PDB observed in patients, linked to increased osteoclastogenic potential and decreased type I IFN production	Wong et al (2020)
PDB	Whole‐body knock‐in of mutant p62P392L	Increased osteoclastogenic potential of bone microenvironment, but histologically normal bones	Hiruma et al (2008)
Sarcopenia	Muscle‐specific deletion of Atg7	Exacerbated muscle loss during denervation and fasting, and abolished sestrin‐mediated protection against disuse‐induced muscle atrophy	Masiero et al (2009), Segales et al (2020)
Sarcopenia	shRNA‐mediated muscle‐specific deletion of 15‐PGDH	Increased aged muscle mass, strength, and exercise performance	Palla et al (2021)
Sarcopenia	Whole‐body deletion of Sesn1	Exacerbated disuse‐induced muscle atrophy after constitutive mTORC1‐signaling activation	Segales et al (2020)
Sarcopenia	Muscle‐specific deletion of Mfn2	Enhanced muscle atrophy and sarcopenia, linked to age‐induced mitochondrial dysfunction and ROS production, after mitophagy inhibition	Sebastian et al (2016)
Sarcopenia	Conditional muscle‐specific deletion of Opa1	Accelerated muscle atrophy linked to a precocious senescence phenotype and premature death	Tezze et al (2017)
Sarcopenia	Whole‐body deletion of Trim32	Exacerbated muscle atrophy associated with impaired autophagic flux	Di Rienzo et al (2019)
XLMTM	Whole‐body deletion of Mtm1	Myopathic defects associated with impaired autophagic flux and abnormal mitochondria	Fetalvero et al (2013)

HFD, high‐fat diet; MSC, mesenchymal stem cell; PC2, type II procollagen; PDB, Paget disease of bone; XLMTM, X‐linked myotubular myopathies.