SummaryThe mechanisms by which early spatiotemporal expression patterns of transcription factors such as Pax6 regulate cortical progenitors in a region-specific manner are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6+/+ and Pax6−/− cortices and identified many negatively regulated cell-cycle genes, including Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes that directly promote the mechanics of the cell cycle, and we found that Pax6 inhibits pRb phosphorylation and represses genes involved in DNA replication. Our results indicate that Pax6’s modulation of cortical progenitor cell cycles is regional and direct.
Objective Domestic Cat Hepadnavirus (DCH) is a novel virus recently identified in the domestic cat. Currently, little is known regarding its clinical significance. The hepadnaviridae family includes the Hepatitis B Virus (HBV). Co‐infection of HBV and Hepatitis C in humans increases the risk of uveitis. We aimed to determine whether DCH is present in the United Kingdom (UK) and whether DCH warrants investigation as a potential cause of uveitis in cats. Procedures Clinical records from the Royal Veterinary College (RVC) and the Animal Health Trust (AHT) were reviewed for feline cases diagnosed with endogenous uveitis. A healthy control group was identified from cats presented to the RVC as blood donors. DNA was extracted from stored blood samples using commercially available kits. Polymerase chain reaction assays were performed to confirm the presence of feline DNA and to detect the presence of DCH DNA using previously described protocols. Results Blood samples were available from 65 cats with endogenous uveitis and 43 healthy control cats. Two blood samples from cats with endogenous uveitis tested positive for the presence of DCH DNA. DCH DNA was not detected in the control group. There was no statistically significant difference between the prevalence of DCH between the groups. Conclusions Domestic Cat Hepadnavirus is present in the UK. This study failed to demonstrate a conclusive link between DCH and uveitis in cats, although further studies to investigate an association with other feline diseases are warranted.
Background In humans, ADAMTS17 mutations are known to cause Weill-Marchesani-like syndrome, which is characterised by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. Breed-specific homozygous mutations in ADAMTS17 are associated with primary open angle glaucoma (POAG) in several dog breeds, including the Petit Basset Griffon Vendeen (PBGV) and Shar Pei (SP). We hypothesised that these mutations are associated with short stature in these breeds. Methods Two hundred thirty-three PBGV and 66 SP were genotyped for their breed-specific ADAMTS17 mutations. The height of each dog was measured at the withers. We used linear (per allele) regression to assess the association between ADAMTS17 mutations and height as a continuous variable, and linear regression and likelihood ratio tests to assess the shape of the association by comparing a general model with a linear (per allele) model. Results The adjusted mean heights of affected, carrier, and clear PBGV were 33.49 cm ( n = 21, 95% CI 32.78–34.19 cm), 34.88 cm ( n = 85, 95% CI 34.53–35.25 cm), and 34.92 cm ( n = 121, 95% CI 34.62–35.21 cm), respectively. The mean heights of affected, carrier, and clear SP were 43.96 cm ( n = 9, 95% CI 41.88–46.03 cm), 47.56 cm ( n = 28, 95% CI 45.50–48.63 cm), and 48.95 cm ( n = 23, 95% CI 47.80–50.11 cm), respectively. There was a significant difference between the height of affected and clear animals in the PBGV ( P = 0.001) and the SP ( P = < 0.0001). Conclusions ADAMTS17 POAG mutations are significantly associated with height in these breeds. Electronic supplementary material The online version of this article (10.1186/s40575-019-0071-6) contains supplementary material, which is available to authorized users.
Purpose The purpose of this study was to investigate the most common causes of endogenous feline uveitis in a UK referral population and to investigate associations based on signalment. Methods Retrospective multicenter cross‐sectional study from 2010 to 2019 including cats presented to the Animal Health Trust and the Royal Veterinary College with clinical signs consistent with uveitis. Cats were included in analyzes if they had a full physical examination including an ophthalmic examination, complete blood count, serum biochemistry, and infectious disease testing for at least two diseases unless the diagnosis was found on clinical examination (eg, neoplasia). Results A total of 92 cats were included in the study. The majority of cats presenting with uveitis were male (66.3%). The most common causes of endogenous uveitis were idiopathic uveitis (42/92 45.7%), feline infectious peritonitis (FIP) 15/92 16.3%), and lymphoma (10/92 10.9%). Fisher's exact test showed differences in breed across diagnosis groups (p = .002) with purebred cats being overrepresented in the lymphoma and FIP groups. Kruskal‐Wallis test showed differences in median age across diagnosis groups (p < .001) with cats in the FIP group having the youngest age (median 1.4 years, interquartile range (IQR) 0.4–1.8 years) and cats in the neoplasia (primary or paraneoplastic) group having the oldest age (median 12.8 IQR 10.8–13.8). Idiopathic uveitis was unilateral in 56.1% of cases, and infectious causes were unilateral in 47.8% of cases. Conclusions The most common cause of endogenous uveitis in a population of cats in the UK was idiopathic uveitis, followed by FIP and lymphoma.
Key Clinical MessageA rhomboid blepharoplasty can be used to achieve functional and cosmetic eyelid reconstruction at the medial canthus in the horse. Combination of a rhomboid blepharoplasty with cryotherapy is a treatment option for eyelid ocular squamous cell carcinomas.
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