Rapid Macrosatellite Evolution Promotes X-Linked Hybrid Male Sterility in a Feline Interspecies Cross.

The sterility or inviability of hybrid offspring produced from an interspecific mating result from incompatibilities between parental genotypes that are thought to result from divergence of loci involved in epistatic interactions. However, attributes contributing to the rapid evolution of these regions also complicates their assembly, thus discovery of candidate hybrid sterility loci is difficult and has been restricted to a small number of model systems. Here we reported rapid interspecific divergence at the DXZ4 macrosatellite locus in an interspecific cross between two closely related mammalian species: the domestic cat (Felis silvestris catus) and the Jungle cat (Felis chaus). DXZ4 is an interesting candidate due to its structural complexity, copy number variability, and described role in the critical yet complex biological process of X-chromosome inactivation. However, the full structure of DXZ4 was absent or incomplete in nearly every available mammalian genome assembly given its repetitive complexity. We compared highly continuous genomes for three cat species, each containing a complete DXZ4 locus, and discovered that the felid DXZ4 locus differs substantially from the human ortholog, and that it varies in copy number between cat species. Additionally, we reported expression, methylation, and structural conformation profiles of DXZ4 and the X chromosome during stages of spermatogenesis that have been previously associated with hybrid male sterility. Collectively, these findings suggest a new role for DXZ4 in male meiosis and a mechanism for feline interspecific incompatibility through rapid satellite divergence.

Assessment of cardiac troponin I and C-reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs.

OBJECTIVE: To report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Twenty client-owned dogs presenting for elective ovariohysterectomy or castration. METHODS: The dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg(-1)) and hydromorphone (0.1 mg kg(-1)) i.m. approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg(-1)) i.v. to effect and in dogs in group 2 with diazepam (0.2 mg kg(-1)) i.v. followed by etomidate (2 mg kg(-1)) i.v. to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5-4%) and group 2 received a combination of fentanyl (0.8 microg kg(-1) minute(-1)) and midazolam (8.0 microg kg(-1) minute(-1)) i.v. plus sevoflurane (adjustable vaporizer setting 0.5-4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively. RESULTS: Baseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma. CONCLUSIONS AND CLINICAL RELEVANCE: There was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.

MicroRNA expression in canine mammary cancer.

MicroRNAs (miRNAs) are 18-22-nt noncoding RNAs that are involved in post-transcriptional regulation of genes. Oncomirs, a subclass of miRNAs, include genes whose expression, or lack thereof, are associated with cancers. Until the last decade, the domestic dog was an underused model for the study of various human diseases that have genetic components. The dog exhibits marked genetic and physiologic similarity to the human, thereby making it an excellent model for study and treatment of various hereditary diseases. Furthermore, because the dog presents with distinct, spontaneously occurring mammary tumors, it may serve as a model for genetic analysis and treatments of humans with malignant breast tumors. Because miRNAs have been found to act as both tumor suppressors and oncogenes in several different cancers, expression patterns of ten miRNAs (miR-15a, miR-16, miR-17-5p, miR-21, miR-29b, miR-125b, miR-145, miR-155, miR-181b, let-7f) known to be associated with human breast cancers were compared to malignant canine mammary tumors (n = 6) and normal canine mammary tissue (n = 10). Resulting data revealed miR-29b and miR-21 to have a statistically significant (p < 0.05 by MANOVA analysis) upregulation in cancerous samples. The ten canine miRNAs follow the same pattern of expression as in the human, except for miR-145 which does not show a difference in expression between the normal and cancerous canine samples. In addition, when analyzed according to specific cancer phenotypes, miR-15a and miR-16 show a significant downregulation in canine ductal carcinomas while miRsR-181b, -21, -29b, and let-7f show a significant upregulation in canine tubular papillary carcinomas.