Biological Role of Dystroglycan in Schwann Cell Function and Its Implications in Peripheral Nervous System Diseases

Table 1

Loss-of-function studies for DGC components.

Disrupted genes (animal)	Expression level and modification of Schwann cell proteins	Nerve pathology and functional deficits	References
Schwann cell-selective Dag1 null mouse (P0-DG null mouse)	No expression of DG; Reduced expressions of other DGC components except periaxin, laminin-2	Mild radial sorting defect in spinal roots; Myelin folding/polyaxonal myelination; Mild loss of myelinated axons in sciatic nerve; Intact BM; Lower conduction; Disruption of nodes; Disrupted Cajal bands; Shortening of internodes	[25, 52, 54]
Unknown (dy mouse)	No expression of laminin 𝛼2; Upregulation of laminin 𝛼4	Radial sorting defect in nerve roots and cranial nerves; Mild radial sorting defect in peripheral nerves; Disrupted BM; Shortening of internodes; Lower conduction; Widened nodes of Ranvier	[55–61]
Lama2/point mutation of LN domain/CxxC motif (dy^nmf417mouse)	Normal expression of the mutated laminin 𝛼2 chain	Radial sorting defect in nerve roots; Intact BM	[62]
Lama2/splicing skip of exon2 (dy2J mouse)	Normal expression of truncated laminin 𝛼2 chain (domain IV deleted); Upregulation of laminin 𝛼4	Radial sorting defect in nerve roots and cranial nerves; Mild radial sorting defect in peripheral nerves; Multiple axons myelinated by one Sc; Disrupted BM; Disrupted Cajal bands; Shortening of internodes	[52, 55, 57, 60, 63–65]
Lama2 (dy3k mouse)	No expression of laminin 𝛼2; Upregulation of laminin 𝛼4	A few solitary unmyelinated axons; Thin myelin sheath; Decreased nodal gap; Lower conduction; Disrupted BM	[66]
Lama4 (mouse)	No expression of laminin 𝛼4	Radial sorting defect in peripheral nerves; Polyaxonal myelination; Intact BM	[67]
Lama2/Lama4 (dy2J/𝛼4 null mouse)	Normal expression of truncated laminin 𝛼2 chain; No expression of laminin 𝛼4	Severe radial sorting defect of peripheral nerves; Mild radial sorting defect in spinal roots; Disrupted BM	[67]
Schwann cell selective Lamg1-null mouse	Severely reduced expression of all known laminin isoforms in Schwann cells	Radial sorting defect in spinal roots and peripheral nerves	[68]
L-Periaxin (mouse)	No expression of L-periaxin	Demyelination in sciatic nerve; Myelin folding; Disrupted S-L incisure; Lower conduction; Impaired regeneration; Hyperalgesia, allodynia; Disrupted Cajal bands; Shortening of internodes	[51, 69]
Utrophin (mouse)	No expression of utrophin	Disrupted Cajal bands; Shortening of internodes	[52]
Sarcoglycans (BIO14.6 hamster)	No expression of sarcoglycans; Reduced expression of 𝛼-DG and Dp116	Myelin folding; Disrupted S-L incisure	[50]
Large null mouse (enr, myd)	Very low expression of Large; Hypoglycosylation of 𝛼-DG	Radial sorting defect in sciatic nerve and spinal roots; Intact BM; Lower conduction; Disrupted Cajal bands; Impaired regeneration	[52, 70]
Fukutin chimera mouse	Deficiency of fukutin; Hypoglycosylation of 𝛼-DG	Radial sorting defect in sciatic nerve and spinal roots; Loss of myelinated axons in nerve roots and sciatic nerve at P15–30; Multiple axons myelinated by one Sc; Intact BM; Disruption of NMJ	[71]
Schwann cell-selective 𝛽1 integrin null mouse	No expression of 𝛽1 integrin	Radial sorting defect in sciatic nerve; Disrupted BM	[72]
Schwann cell-selective 𝛽4 integrin null mouse	No expression of 𝛽4 integrin	Myelin folding	[54]
Schwann cell-selective 𝛽4 integrin/Dag1 null mouse	No expression of DG and 𝛽4 integrin	Radial sorting defect in spinal ventral roots; Severe myelin folding; Demyelination; Disrupted BM	[54]

BM: basement membrane, DG: dystroglycan, S-L: Schmidt-Lanterman, NMJ: neuromuscular junction, Sc: Schwann cell.