FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice.

Fancj, the gene associated with Fanconi anemia (FA) Complementation Group J, encodes a DNA helicase involved in homologous recombination repair and the cellular response to replication stress. FANCJ functions in part through its interaction with key DNA repair proteins, including MutL homolog-1 (MLH1), Breast Cancer Associated gene-1 (BRCA1), and Bloom syndrome helicase (BLM). All three of these proteins are involved in a variety of events that ensure genome stability, including the events of DNA double strand break (DSB) repair during prophase I of meiosis. Meiotic DSBs are repaired through homologous recombination resulting in non-crossovers (NCO) or crossovers (CO). The frequency and placement of COs are stringently regulated to ensure that each chromosome receives at least one CO event, and that longer chromosomes receive at least one additional CO, thus facilitating the accurate segregation of homologous chromosomes at the first meiotic division. In the present study, we investigated the role of Fancj during prophase I using a gene trap mutant allele. Fancj (GT/GT) mutants are fertile, but their testes are very much smaller than wild-type littermates, predominantly as a result of impeded spermatogonial proliferation and mildly increased apoptosis during testis development in the fetus. This defect in spermatogonial proliferation is consistent with mutations in other FA genes. During prophase I, early events of synapsis and DSB induction/repair appear mostly normal in Fancj (GT/GT) males, and the FANCJ-interacting protein BRCA1 assembles normally on meiotic chromosome cores. However, MLH1 focus frequency is increased in Fancj (GT/GT) males, indicative of increased DSB repair via CO, and is concomitant with increased chiasmata at diakinesis. This increase in COs in the absence of FANCJ is associated with increased localization of BLM helicase protein, indicating that BLM may facilitate the increased rate of crossing over in Fancj (GT/GT) males. Taken together, these results demonstrate a critical role for FANCJ in spermatogenesis at two stages: firstly in the proliferative activity that gives rise to the full complement of testicular spermatogonia and secondly in the establishment of appropriate CO numbers during prophase I.

Incidence and risk factors for canine mastitis and metritis in two guide dog populations.

Canine mastitis and metritis can cause severe illness but the incidence and risk factors have not been well-studied. Goals in the present study were: 1) report the incidence of mastitis and metritis in a large population, and 2) identify potential risk factors that predispose females to those diseases. A retrospective cohort study was conducted using data from two guide dog colonies that was collected for 17 and 10 years, respectively, for the two colonies. A total of 3076 whelpings occurred during the respective study periods and data were analyzed. Clinical mastitis was diagnosed in 13.2 % of whelpings (408 cases) with the average day of diagnosis being 16.7 postpartum. Risk factors for mastitis identified were colony, litter size where bitches that had large litter size of ≥9 pups (16.2 %) were 60 % more likely to develop mastitis compared with bitches that had litters of <9 pups (11.3 %). Bitches with congestion of the mammary gland were 4.8 times more likely to develop mastitis compared with bitches without mammary congestion. Case incidence of metritis was small (0.7 % of whelpings) and occurred on average at day-5 postpartum (range 1-16). There were no significant risk factors identified, and this may be due to the small number of metritis cases (22 cases) in the present study. Interpretations regarding metritis, therefore, should be made with caution. The results from this study provide parameters for breeders and veterinarians to identify bitches that may require close monitoring for mastitis and metritis.

Identifying risk factors for canine dystocia and stillbirths.

Canine dystocia is a common problem that increases the risk of mortality to the dam and stillbirths for the pups. Understanding the risk factors for dystocia and stillbirth can help guide decision making to improve outcomes of whelping management. This study aimed to 1) evaluate risk factors for canine dystocia; and 2) assess risk factors for stillbirth in puppies, by examining all whelpings and puppies born in two breeding populations of guide dogs for a defined period of time. Dystocia risk factors were evaluated using a repeated measures model on 2,489 litters with an overall dystocia rate of 23.8%. Risk factors identified for dystocia were colony, litter size, and age of dam. Small litter size (<5 pups) had the highest dystocia rate of 36.5%, large litter size (>9 pups) had an intermediate dystocia rate of 26.9% and medium litter size had the lowest dystocia rate of 22.1%. Dystocia risk increased as the age of dam increased. Stillbirth risk factors were evaluated for 19,577 pups and the overall stillbirth rate was 5.9%. Risk factors identified for stillbirths were dystocia, litter size, cesarean section performed and breed. Pups from litters that had dystocia were 2.35 times more likely to be stillborn compared with normal litters born without dystocia. Stillbirth risk increased as litter size increased. Pups from litters of 11 or more pups were 1.45 times more likely to be stillborn. Specific information was available for a subset of pups and was used to evaluate the association with stillbirth. Low birth weight was associated with increased stillbirth risk but large pups were also at higher risk of stillbirth compared with average size pups. Stillborn pups had longer mean (102 vs 65 min) and median (47 and 32 min) inter-pup intervals compared with live pups. The positive predictive values for stillbirth were 13.5%, 28.4%, 31.8% and 36.5% when inter-pup interval threshold was set at 1, 2, 3 and 4 h respectively. There is a tradeoff between over diagnosing stillbirth and increased positive predictive value for stillbirth when inter-pup interval threshold is extended but the improvements were modest after 2 h. The last pup born in a litter regardless of litter size was significantly more likely to be stillborn. In conclusion, this paper details data driven parameters to use when making the decision to intervene during whelping that optimize survival for dams and puppies.