Table 1.

Transgenic mouse models with Meibomian gland alterations and/or Meibomian gland dysfunction (MGD)-like features *.

Model	Description	Animal	MGD Features	Other Defects
Yagyu, H. et al. 2000.	Elimination of Acyl-CoA:cholesterol acyltransferase gene 1 (ACAT-1).	ACAT-1 null (ACAT-1−/−) mice	Narrow eye fissures and Meibomian gland atrophy.	Lipid-depleted adrenal glands and corneal erosion.
Pikus et al. 2004.	Modulation of bone morphogenic protein (BMP).	K14-Noggin transgenic mouse	Formation of pilosebaceous units at the expense of Meibomian glands/suppression of the induction of Meibomian glands.	Abnormal sweat glands, ectopic cilia, distal limb agenesis, hyperpigmentation of claws, interdigital webbing, and reduced footpads.
Cascallana et al. 2005.	Overexpression of glucocorticoid receptor (GR).	keratin 5 (K5)-GR mice	Lack of Meibomian glands.	Underdeveloped sweat glands and preputial glands, and abnormal hair follicles, teeth, and palate.
Cui, C.Y. et al. 2005; Cui, C.Y. et al. 2010; Wang, Y.C. et al. 2016; Li, S. et al. 2018.	Mutation of X-linked anhidrotic ectodermal dysplasia (EDA) gene.	Eda mutant (Eda−/−) Tabby mice	Lack of Meibomian glands, reduced tear break up times, and blepharitis.	Corneal neovascularization, ulceration, keratinization, reduced corneal epithelial microvilli, and conjunctivitis.
Vauclair, S. et al. 2007.	Skin-specific inactivation of the Notch1 gene.	Notch1K14Cre mice; Notch1 K5CreERT mice	Meibomian gland dysfunction, abnormal morphology of Meibomian glands, lack of lipids in meibocytes.	Eye irritations, corneal opacity and keratinization.
Chang et al. 2009.	Elevation of EDAR signaling.	EdarTg951 heterozygous transgenic and EdarTg951/Tg951 homozygous transgenic mice	Enlarged Meibomian glands.	Excessively branched mammary and salivary glands.
Tukel, T. et al. 2010.	Homozygous TWIST2 (MIM 607556) nonsense mutations.	Twist2 knockout (KO) mice	Absence of or hypoplastic Meibomian glands and decreased eyelash follicles.	Bitemporal lesions, narrow snout, pointed chin, and sparse or absent eyelashes.
Kenchegowda, D. et al. 2011.	Conditional deletion of Krüppel-like factor (KLF) 5.	Klf5-conditional null (Klf5CN) mice	Malformed Meibomian glands with disorganized acini, lipid accumulation in the Meibomian ducts.	Smaller eyeballs; translucent and thicker corneas with a defective epithelial basement membrane and hypercellular stroma; conjunctivas lacking goblet cells.
Tsau, C. et al. 2011.	Deletion of the sequences encoding the homeodomain and C-terminal region of Barx2.	Barx2-null mice	~50% of Barx2–/– mice have eyelid fusion problems, smaller eyes, and defects in Meibomian gland development and structure including Meibomian gland drop out or smaller glands.	Defective lacrimal gland morphogenesis, and absence of the harderian gland.
Lin et al. 2013.	Mice lacking fatty acid transport protein (FATP) 4.	Tg (IVL-Fatp4) transgenic mice	Underdeveloped Meibomian glands with thickened ducts.	Abnormal sebaceous glands, and thick skin with defective barrier.
McMahon et al. 2014.	Mutation in ELOVL4 resulted in abnormal synthesis of extremely long-chain fatty acids.	Heterozygous Stgd3 mice, on a mixed 129SvEv and C57BL6 background	Protruding Meibomian gland orifice, intragland anatomical changes, toothpaste-like meibum, and intense staining for ELOVL4 in glands.	Inability to open eyes fully, and increased blink rates.
Chen, Z.Y. et al. 2014.	Conditional deletion of Sox9.	Sox9CKO mice	Reduced number of Meibomian glands, 40% fewer glands in the upper and lower eyelids, and most Meibomian glands have fewer acini.	Lacrimal gland (LG) deficiency and abnormal LG morphogenesis, absence of harderian glands, and hair loss in mouse eyelids and facial skin.
Meng, Q. et al. 2014.	Targeted gene ablation that inactivated distinct signaling pathways.	Map3k1-null and Dkk2-null mice, K14rtTA/tet-O-cre/Shp2F/F mice, c-JunΔ/ΔOSE and EgfrΔ/ΔOSE mice, Map3k1/Jnk1 and Map3k1/Rhoa compound mutants	Eyelid fusion problems and severe hypoplastic Meibomian glands.	Corneal erosion/ulceration, harderian gland hypoplasia, misplacement of extraocular muscles and eyes open at birth.
Ibrahim, O.M. et al. 2014; Ikeda et al. 2018.	Deficient in Cu/Zn superoxide dismutase (SOD1) leading to accumulation of reactive oxygen species (ROS).	Sod1−/− mice	Age-related Meibomian gland abnormalities including an increase in periglandular inflammatory infiltrates, decrease in Meibomian gland glandular acinar density, and increase in periglandular fibrosis.	Corneal fluorescein and lissamine staining evidencing corneal erosions and reduced tear secretion.
Dong, F. et al. 2015.	Conditional inducible ablation of TGFα in the eyelid.	Bi-transgenic Kera-rtTA/tetO-TGFα (KR/TG) mice	Abnormal Meibomian glandmorphogenesis, Meibomian gland atrophy, and eyelid tendon and tarsal plate malformation.	Precocious eye opening, swollen eyelids, and conjunctival eyelid epithelial hyperplasia.
Sima, J. et al. 2016; Cui, C.Y. et al. 2010.	Evaluation of Dickkopf 4 (DKK4) regulated signaling pathway.	Skin-specific Dkk4 transgenic mice (WTDk4TG, wildtype background) and TaDk4TG (Tabby background)	Meibomian gland formation defects in Dkk4Tg mice, similar with Tabby mice.	Cataracts, corneal blindness and rough hair coat.
Miyake et al. 2016.	HR-AD diet (a special diet with limited lipid content).	HR-1 hairless mice (fed with HR-AD diet)	Plugged Meibomian gland orifice, Meibomian gland ductal epithelial hyperkeratinization and acinar atrophy.	No other phenotypes recorded.
Reneker, L.W. et al. 2017; Chen, Z.Y. et al. 2014.	Conditional inducible ablation of FGFR2.	Inducible Fgfr2CKO mice	Macerated periorbital hairs and eyelids, Meibomian gland orifice obstruction, reduced volume of meibum and Meibomian gland acinar atrophy.	Ocular irritation and rubbing.
Yu, D. et al. 2018.	Deletion of epithelial sodium channel (ENaC) functional subunits in the Meibomian gland.	Conditional βENaC Meibomian gland knockout (KO) mouse (βENaCfl/fl;Shh-Cre+/−)	Age-dependent, female-predominant Meibomian gland dysfunction (obstruction of Meibomian gland orifices and Meibomian gland acinar atrophy).	Increased tear secretion and severe ocular surface damage (corneal opacity, ulceration, neovascularization and ectasia).
Swirski, S. et al. 2018.	Mutations in the gene encoding Gasdermin A3 (Gsdma3).	C+/H− Mice	Degeneration of Meibomian glands, increased eyelid tissue formation and eyelid closure.	Progressive hair loss, hyperkeratinization of the skin, degeneration of sebaceous glands, corneal opacity, and corenal vascularization.
Sassa, T. et al. 2018.	Gene disruption of Elovl1 resulted in insufficient elongation of FAs.	Elovl1−/− Tg(IVL-Elovl1) mice	Evaporative dry eye phenotype with increased eye-blink frequency, together with partially closed eyes and excessive tear production.	Corneal opacity, vascularization and epidermalization in aged mice.
Sun, M. et al. 2018; Gesteira, T.F. et al. 2017.	Targeted knockout of Hyaluronan synthase (Has) genes 1, 2 and 3.	Combined Has1−/−;Has3−/− mice; conditional Has2Δ/ΔMG mice	Meibomian gland hyperplasia with more branched, longer and wider acini.	Dysmorphic eyelids with conjunctival epithelial hyperplasia and thinner corneal thickness.
Swirski, S. et al. 2018; Miyazaki, M. et al. 2001.	Targeted knockout of Stearoyl-CoA desaturase (SCD) 1.	SCD-1 knockout mice (SCD-1−/−)	Narrow eye fissures, atrophy or loss of Meibomian glands and depletion of meibum lipids.	Cutaneous abnormalities including thinner hair coat and hair loss, with atrophic sebaceous gland abnormalities and compensatory increases in tear volume and mucin levels.
Sundberg, J.P. et al. 2018.	Null mice for fatty acyl CoA reductase 2 (Far2) gene altering saturated 16:0 and 18:0 carbon fatty acids.	Homozygous mutant Far2tm2b(KOMP)Wtsi/2J (Far2−/−; null)	Markedly dilated Meibomian gland ducts, and abnormal sebocytes with clustered eosinophilic remnants.	Patchy alopecia on the dorsal trunk and diffuse hair thinning on the ventral body surface.
Butovich, I.A. et al. 2019.	Loss of ELOVL3 altering the synthesis of C21:0-C29:0 fatty acids.	Elovl3 knockout (E3hom) mice	Delayed eye opening, weeping eyes, crusty eyelids, eyelid edema, highly vascularized cornea and tarsal plates (TPs), slit eye, and excessive tearing.	Hairless pups and greasy fur in adults.
Wu, L. et al. 2019.	Null SDR16C5 and SDR16C6 mice with altered retinoic acid (RA) biosynthesis.	Sdr16c5/Sdr16c6 double-knockout mice (DKO)	Both the upper and lower eyelids are thicker and longer (eyelid expansion) with larger Meibomian glands.	Accelerated hair regrowth.
Widjaja-Adhi, M.A.K. et al. 2020.	Ablation of Acyl-CoA wax alcohol acyltransferase 2 (AWAT2) enzymatic activity.	Awat2-knockout mice (Awat2−/−)	Obstruction of the orifice and excretory duct of Meibomian glands, hyperkeratinization of the epithelium, absence of wax esters and overproduction of cholesteryl esters.	Shorter tear film break-up time, deterioration of the corneal surface, granular deposits in the corneal stromal layer, corneal neovascularization, blepharitis, Iritis, scaly and dry skin, and smaller sebaceous glands.

* This table summarizes findings from studies published between 2000 and 2020, which have been ordered chronologically.