Table 1.

Animal models used to investigate age-associated intervertebral disc degeneration

Mouse models
Gene symbol	Gene name/description	Protein function	Model	Age-related disc degenerative changes	Ref
Ercc1	Excision repair cross-complementing rodent repair 1	DNA repair	M	Systemic ERCC1-deficiency accelerated age-dependent disc degeneration	28
n/a	Senescence-accelerated mouse (SAM)	Gene not yet identified	Derived from AKR/J	Amyloid deposition in disc AF, articular cartilage	221
DmdMdx	X-chromosome-linked muscular Dystrophy	Dystrophin-skeletal muscle integrity	M	Age-related loss of disc proteoglycan	222
Cnn2	Connective tissue growth factor (CTGF or CCN2)	Matricellular protein involved in cellular adhesion, migration, ECM synthesis	TG	Notochord-specific CCN2 deletion accelerated age-dependent disc degeneration	223
Bgn	Biglycan	Small leucine repeat proteoglycans ECM	TG	Age-related early onset of disc degeneration	224
Ky	Kyphoscoliosis peptidase	Cytoskeleton-associated protease required for normal muscle growth	ARM	Degenerative changes in cervical and thoracic discs; kyphosis	225
Skt	Sickle tail	Linked to Danforth’s short tail locus	TG	Abnormal development of the intervertebral disc	226
n/a	Danforth’s short tail locus (Sd)	Gene not yet identified	M, SD	Aberrant patterns of vertebrae and disc development	227
C57Bl6	Wildtype mice	Natural aging mice		Natural aging-related disc degeneration	228

Other animal models
Animals	Scientific name	Key features & analysis methods	Age-related disc degenerative changes	Ref
Hamster	Cricetinae	Chinese hamsters prone to development of spontaneous diabetes. Spines of age 10–33 months histologically analyzed	Aging changes in intervertebral discs Spondylosis was present at an earlier age in diabetic than in nondiabetic hamster.	229
Rat	Rattus	Male Fisher 344 rats. μCT of spines of age 3, 12, 18, 30 months	Age-associated morphometric and degenerative disc changes	230
Sand rat	Psammomys obesus	Spontaneous development of diabetes. Age 1–46 months analyzed radiographically and histologically	Age-related and diabetes-related spontaneous development of lumbar disc degeneration	231
Rabbit	Oryctolagus cuniculus	New Zealand White rabbits. Age 1–30 months studied by MRI, histology, gene expression	Natural aging-related disc degeneration	232
Pig	Sus scrofa domesticus	Porcine discs of age 2–3 weeks, 6–9 month, 2–3 years analyzed by histology, GAG assay, cell density assay, gene expression	Disc MMP-1 increased with age. GAG and collagen I, II, aggrecan decreased with age.	219
Dog	Canis lupus familiaris	Discs of chondrodystrophic (CD) and nonchondrodystrophic(NCD) dogs of age 1–7 years were analyzed by histology, GAG, and MMP activity	CD dogs showed early age onset of disc degenerative changes compared to NDC dogs.	233
Sheep	Ovis aries	Discs of new-born, 3, 12, and >36 months were analyzed mechanically and microscopically to assess nucleus pulposus-endplate integration	Rapid increase in NP-EP insertion nodes between birth and 3 months, after which this integration remained constant.	234
Alpaca	Vicugna pacos	Young (2–6 years) and older (>10 years) alpaca underwent MRI evaluation to detect cervical spine degeneration	No cervical disc degeneration in young alpacas. Increased disc degeneration incidence and severity at lower cervical levels in older alpacas	235
Rhesus Macaques	Macaca mulatta (Macaques monkeys)	Longitudinal study of macques 11–32 years of age to assess disc space narrowing (DSN) by radiography.	Age-associated disc space narrowing, osteophytosis, increased disc tissue stiffness	236

Genetic models: Mutation (M), Transgenic (TG), Autosomal recessive mutation (ARM), Truncation mutation (TM). N/A: not applicable.