Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH.

Equine Cerebellar Abiotrophy (CA) is a neurological disease found in Arabian horses. CA is characterized by post-natal degeneration of the Purkinje cells of the cerebellum. Signs of CA include ataxia, head tremors, and a lack of balance equilibrium. We have discovered a linkage of the CA phenotype to a microsatellite marker on ECA2 and identified a region of conserved homozygosity spanning approximately 142 kb. Complete sequencing of the four genes in this region identified one SNP found only in Arabian horses, located in exon 4 of TOE1 and approximately 1200 base pairs upstream of MUTYH, adjacent to a possible binding site for the transcription factor GATA2. qPCR analysis of cDNA from the cerebella of affected and unaffected horses suggested that MUTYH expression is down-regulated in affected horses. This SNP may therefore have a function effect on TOE1, or a regulatory effect on MUTYH by negatively affecting the binding affinity of GATA2.

Azoospermia associated with bilateral segmental aplasia of the ductus deferens in a stallion.

A 3-year-old Quarter Horse halter stallion was referred for routine semen evaluation. Physically, the stallion's reproductive organs appeared normal. Repeated semen evaluations did not reveal any spermatozoa. Because high activities of alkaline phosphatase are detected in the epididymal fluid and indicative of complete ejaculation, alkaline phosphatase activities were analyzed in several samples, which yielded activities far less than reference values and suggested a blockage of the reproductive tract. Endoscopic evaluation of the urethra and the bulbourethral, prostate, and urethral gland ducts did not reveal abnormalities. The left ductus deferens was exposed surgically, and attempts to pass a catheter through it in a normograde direction met resistance after 20 cm. Laparoscopic abdominal surgery revealed the ductus deferens tapered to a thin structure just cranial to the entrance in the urogenital fold, cranial and lateral to the bladder. Both ductus deferentia were similarly affected. The symmetry and bilateral nature of the abnormalities were strong indications of a possible congenital defect.

Inheritance of cerebellar abiotrophy in Arabians.

OBJECTIVE: To determine the mode of inheritance for cerebellar abiotrophy (CA), a neurologic disease in Arabians. ANIMALS: 804 Arabians, including 29 horses (15 males and 14 females) with CA. PROCEDURES: Most horses (n = 755) belonged to 1 of 4 paternal families. Among the 29 CA-affected horses, all had clinical signs consistent with the disease; the disease was confirmed histologically following euthanasia in 8 horses. From the pedigree information, inbreeding coefficients were calculated for 16 affected horses and compared with coefficients for a subgroup of 16 unaffected horses. Complex segregation analysis was used to determine the effect of a putative Mendelian locus on the development of the disease and the probable mode of inheritance of CA. RESULTS: The mean inbreeding coefficient was 0.0871 for CA-affected and unaffected horses, suggesting that all of the Arabians were inbred to the same degree and that affected horses were not more inbred than were unaffected horses. Results of the complex segregation analysis were consistent with a single Mendelian autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of the mode of inheritance of CA should help breeders to make informed decisions regarding the selection of animals for mating when closely related horses have developed CA or produced CA-affected foals.