Effect of distal ulnar ostectomy on carpal joint stability during weight bearing in the dog.

OBJECTIVE: To assess the influence of a 50% distal ulnectomy on mediolateral carpal stability in the dog. STUDY DESIGN: Canine cadaveric study. SAMPLE POPULATION: Seven canine thoracic limbs METHODS: Thoracic limbs were placed in a jig to mimic weight bearing with a load representing 30% of body weight. Carpal extension angle was standardized at 190° ± 5°. Frontal plane carpal angles were measured with the limb loaded on craniocaudal radiographs before and after ulnectomy. Valgus and varus stress radiographs with the limb loaded were acquired before and after ulnectomy. The limbs were palpated and were subjectively graded for valgus or varus instability by 2 investigators before and after ulnectomy. RESULTS: Mean (±SD) valgus angulation increased after ulnectomy (2.1° ± 1.7°; P = .017; CI95 = 0.5°-3.7°) when the limb was loaded without valgus or varus stress applied. Mean valgus angulation increased after ulnectomy (2.7° ± 2.8°; P = .032; CI95 = -0.2°-5.5°) when valgus stress was applied to the loaded limb. Varus angulation was unchanged after ulnectomy (0.6° ± 4.6°; P = .383; CI95 = -4.2°-5.3°) when varus stress was applied to the loaded limb. Palpation detected increased valgus score after ulnectomy. CONCLUSION: Distal ulnectomy with excision of the lateral styloid process induces a slight increase in valgus in canine cadaver carpi. The clinical consequences of that valgus on carpal function and health should be assessed in clinical patients.

Transfer of the alpha 5(IV) collagen chain gene to smooth muscle restores in vivo expression of the alpha 6(IV) collagen chain in a canine model of Alport syndrome.

X-linked Alport syndrome is a progressive renal disease caused by mutations in the COL4A5 gene, which encodes the alpha 5(IV) collagen chain. As an initial step toward gene therapy for Alport syndrome, we report on the expression of recombinant alpha 5(IV) collagen in vitro and in vivo. A full-length cDNA-encoding canine alpha 5(IV) collagen was cloned and expressed in vitro by transfection of HEK293 cells that synthesize the alpha1(IV) and alpha2(IV), but not the alpha 3(IV) to alpha 6(IV) collagen chains. By Northern blotting, an alpha 5(IV) mRNA transcript of 5.2 kb was expressed and the recombinant protein was detected by immunocytochemistry. The chain was secreted into the medium as a 190-kd monomer; no triple helical species were detected. Transfected cells synthesized an extracellular matrix containing the alpha1(IV) and alpha2(IV) chains but the recombinant alpha 5(IV) chain was not incorporated. These findings are consistent with the concept that the alpha 5(IV) chain requires one or more of the alpha 3(IV), alpha 4(IV), or alpha 6(IV) chains for triple helical assembly. In vivo studies were performed in dogs with X-linked Alport syndrome. An adenoviral vector containing the alpha 5(IV) transgene was injected into bladder smooth muscle that lacks both the alpha 5(IV) and alpha 6(IV) chains in these animals. At 5 weeks after injection, there was expression of both the alpha 5(IV) and alpha 6(IV) chains by smooth muscle cells at the injection site in a basement membrane distribution. Thus, this recombinant alpha 5(IV) chain is capable of restoring expression of a second alpha(IV) chain that requires the presence of the alpha 5(IV) chain for incorporation into collagen trimers. This vector will serve as a useful tool to further explore gene therapy for Alport syndrome.