Absence of cardiovascular manifestations in a haploinsufficient Tgfbr1 mouse model

Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease belonging to the spectrum of transforming growth factor β (TGFβ)-associated vasculopathies. In its most typical form it is characterized by the presence of hypertelorism, bifid uvula/cleft palate and aortic aneurysm and/or arterial tortuosity. LDS is caused by heterozygous loss of function mutations in the genes encoding TGFβ receptor 1 and 2 (TGFBR1 and -2), which lead to a paradoxical increase in TGFβ signaling. To address this apparent paradox and to gain more insight into the pathophysiology of aneurysmal disease, we characterized a new Tgfbr1 mouse model carrying a p.Y378*nonsense mutation. Study of the natural history in this model showed that homozygous mutant mice die during embryonic development due to defective vascularization. Heterozygous mutant mice aged 6 and 12 months were morphologically and (immuno)histochemically indistinguishable from wild-type mice. We show that the mutant allele is degraded by nonsense mediated mRNA decay, expected to result in haploinsufficiency of the mutant allele. Since this haploinsufficiency model does not result in cardiovascular malformations, it does not allow further study of the process of aneurysm formation. In addition to providing a comprehensive method for cardiovascular phenotyping in mice, the results of this study confirm that haploinsuffciency is not the underlying genetic mechanism in human LDS

A topographic anatomical study of the equine epiploic foramen and comparison with laparoscopic visualisation

Reasons for performing study: There are no previous studies correlating the anatomy of the equine epiploic foramen and its defining structures with laparoscopic images. Objectives: The purpose of this study was to describe the precise anatomy of the epiploic foramen and omental vestibule, to quantify the dimensions of the epiploic foramen and to relate these findings to laparoscopic images. Study design: Descriptive study of cadaver material and laparoscopic images. Methods: Thirty-two horses subjected to euthanasia for reasons unrelated to colic were studied. Two cadavers were used to make vascular casts of the coeliac artery and portal vein. In 30 cadavers the epiploic foramen and omental vestibule were cast with a polyurethane prepolymer immediately after euthanasia. The cast served as a landmark during dissection and the circumference of the epiploic foramen was measured from these casts. Histology was performed on structures defining the epiploic foramen in 2 horses. Laparoscopic images from 6 standing right flank procedures were reviewed. Results: The defining structures of the epiploic foramen and omental vestibule are the hepatoduodenal ligament, hepatogastric ligament and the gastropancreatic and hepatopancreatic folds. The hepatoduodenal ligament has a secondary fold which forms the ventral border of the epiploic foramen, consisting of a central connective tissue core of mainly elastin fibres. The hepatic artery for part of its course is incorporated in the hepatoduodenal ligament. All these structures are clearly visible laparoscopically. The mean circumference of the epiploic foramen is 11.6 2.6cm and its circumference is positively correlated with body weight but is unrelated to age or gender. Conclusions: Several clinically relevant structures delineate the epiploic foramen. Its defining structure consists, in part, of elastin fibres. Anatomical and laparoscopic knowledge may assist surgeons in developing interventions to treat diseases involving the epiploic foramen