Mesioversion of the upper canines in Shelties

Mesioversion of the upper canines (MCM) is a dental anomaly in which the upper canine is displaced forward toward the nose. One or both upper canines may be affected. Typical clinical manifestations include traumatic occlusion, where the incorrect position of the tooth damages soft tissues or other teeth, ulcerations on the upper lip, and an increased risk of periodontal disease. In more severe cases, extraction of the affected tooth or orthodontic correction of its position is required.

In Shetland Sheepdogs, this defect is associated with two genetic variants in two closely located genes: a substitution in the FTSJ3 gene, which encodes an RNA methyltransferase and represents the main genetic factor for mesioversion of the upper canines (MCM), and an insertion in the GH1 gene, which encodes growth hormone and influences the dog’s body size. The association of GH1 with MCM is likely due to its tight genetic linkage with FTSJ3 and its modifying effect on the phenotype. It is not yet precisely known whether these variants act together as a haplotype or each separately.

Dogs homozygous for the FTSJ3 variant have a high risk of MCM regardless of body weight. In individuals heterozygous for the FTSJ3 variant, the risk of developing MCM is related to body weight; lighter dogs have a higher risk than heavier ones. The GH1 variant alone does not cause MCM, but individuals homozygous for this mutation have reduced body size, while heterozygotes show a mild reduction in size. Dogs that are heterozygous for both variants combine an increased risk of MCM with reduced body size, with the dog’s weight modulating the probability of MCM manifestation. Individuals homozygous for both variants show a high risk of MCM together with reduced body size, reflecting the combined influence of both genes.

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References:

Abrams, S.R., Hawks, A.L., Evans, J.M., Famula, T.R., Mahaffey, M., Johnson, G.S., Mason, J.M., Clark, L.A. : Variants in FtsJ RNA 2'-O-Methyltransferase 3 and Growth Hormone 1 are associated with small body size and a dental anomaly in dogs. Proc Natl Acad Sci U S A 117:24929-24935, 2020. Pubmed reference: 32958658.