Ventral Body Wall Research Articles

In-frame deletion of SPECC1L microtubule association domain results in gain-of-function phenotypes affecting embryonic tissue movement and fusion events.

Patients with autosomal dominant SPECC1L variants show syndromic malformations, including hypertelorism, cleft palate and omphalocele. These SPECC1L variants largely cluster in the second coiled-coil domain (CCD2), which facilitates association with microtubules. To study SPECC1L function in mice, we first generated a null allele (Specc1lΔEx4) lacking the entire SPECC1L protein. Homozygous mutants for these truncations died perinatally without cleft palate or omphalocele. Given the clustering of human variants in CCD2, we hypothesized that targeted perturbation of CCD2 may be required. Indeed, homozygotes for in-frame deletions involving CCD2 (Specc1lΔCCD2) resulted in exencephaly, cleft palate and ventral body wall closure defects (omphalocele). Interestingly, exencephaly and cleft palate were never observed in the same embryo. Further examination revealed a narrower oral cavity in exencephalic embryos, which allowed palatal shelves to elevate and fuse despite their defect. In the cell, wild-type SPECC1L was evenly distributed throughout the cytoplasm and colocalized with both microtubules and filamentous actin. In contrast, mutant SPECC1L-ΔCCD2 protein showed abnormal perinuclear accumulation with diminished overlap with microtubules, indicating that SPECC1L used microtubule association for trafficking in the cell. The perinuclear accumulation in the mutant also resulted in abnormally increased actin and non-muscle myosin II bundles dislocated to the cell periphery. Disrupted actomyosin cytoskeletal organization in SPECC1L CCD2 mutants would affect cell alignment and coordinated movement during neural tube, palate and ventral body wall closure. Thus, we show that perturbation of CCD2 in the context of full SPECC1L protein affects tissue fusion dynamics, indicating that human SPECC1L CCD2 variants are gain-of-function.

Cranial translation of the elevated prepuce in dogs before and after two modifications: A cadaveric study.

To quantify cranial translation of the prepuce after elevating it from the ventral body wall and to compare it to the cranial translation achieved after each of two modifications expected to increase cranial translation. Cadaveric study. Ten male dogs. All procedures were performed with dogs in dorsal recumbency. A urinary catheter with an attached millimeter scale was secured in the urethra and the penis was sutured to the ventral body wall to eliminate relative movement between the penis and prepuce. Three preplaced sutures between the prepuce and linea alba, at increasing distances from the prepuce, were used to translate the prepuce cranially. The prepuce was tested after elevating it from the ventral body wall, and after sequentially releasing the skin caudal to the prepuce (modification 1) and the attachment of the lamina interna to the penis (modification 2). The preplaced sutures were tightened and loosened sequentially from caudal to cranial, and the location of the dorsal aspect of the preputial opening on the millimeter scale was noted prior to, and after tightening each of the sutures. Maximum mean (range) cranial translation of the prepuce after elevating the prepuce, and after modifications 1 and 2, was 15 mm (5-26 mm), 25 mm (15-30 mm), and 37 mm (24-50 mm), respectively. Modifications described increased cranial translation of the prepuce. Modifications described in this study may provide alternate strategies for the treatment of dogs with severe paraphimosis.

Musculoskeletal anatomy and nomenclature of the mammalian epipubic bones.

Despite the well-established anatomy nomenclature for the marsupial skeleton, there are no names for the epipubic bone structures. Epipubic bones are paired bones articulating with the pubis and projecting cranially in the ventral body wall, present on the pelvic girdle of cynodonts, monotremes and marsupials. These bones were commonly thought to be related to pouch support in marsupials and more recently associated with locomotion. The parts of the epipubic bones have not been named and this has impeded proper morphological analysis. We analyzed the epipubic bones of 302skeletons comprising American and Australian marsupials, as well as 27monotreme skeletons, and dissected 10marsupials for myological attachments analysis. We suggest the following nomenclature for the epipubic bone structures: crest for the cranial end, shaft for the body of the bone, lateral tubercle and the medial articular process. Some markings on the epipubic bone include the oblique line, pertaining to the attachment of external abdominal oblique muscle from the opposite side. The pyramidalis line is the suggested nomenclature for the pyramidalis muscle attachment and the inguinal ligament line for the inguinal ligament attachment. Regarding myology and attachments, based on dissections and review of the literature, the muscles pyramidalis, pectineus, external and internal abdominal oblique, transversus abdominis and rectus abdominis and the structures linea alba, linea semilunaris and the inguinal ligament are connected to the epipubic bone. As has been previously noted, anatomically, epipubic bones are so named due to their position (epi-above, pubic-pubis), and the same applies to structures such as the "epipubic process" or "epipubic cartilage" in amphibians and reptiles. While testing epipubic bone homology in vertebrates is beyond the scope of this work, we believe that using "epipubic bones" or epipubic cartilage/process as standardized terms for the structures found in the most cranial part of the superior ramus of the pubis would facilitate better anatomical communication. This should be valid for other similar terms, such as "epipubes" or "prepubis", that might occur in the literature in relation to this same physiographic position, and it should also be named as epipubic. We believe that this nomenclature will help in future morphologic studies.

Caldesmon ablation in mice causes umbilical herniation and alters contractility of fetal urinary bladder smooth muscle.

The actin-, myosin-, and calmodulin-binding protein caldesmon (CaD) is expressed in two splice isoforms: h-CaD, which is an integral part of the actomyosin domain of smooth muscle cells, and l-CaD, which is widely expressed and is involved in many cellular functions. Despite extensive research for many years, CaD's in vivo function has remained elusive. To explore the role of CaD in smooth muscle contraction in vivo, we generated a mutant allele that ablates both isoforms. Heterozygous animals were viable and had a normal life span, but homozygous mutants died perinatally, likely because of a persistent umbilical hernia. The herniation was associated with hypoplastic and dysmorphic abdominal wall muscles. We assessed mechanical parameters in isometrically mounted longitudinal strips of E18.5 urinary bladders and in ring preparations from abdominal aorta using wire myography. Ca2+ sensitivity was higher and relaxation rate was slower in Cald1-/- compared with Cald1+/+ skinned bladder strips. However, we observed no change in the content and phosphorylation of regulatory proteins of the contractile apparatus and myosin isoforms known to affect these contractile parameters. Intact fibers showed no difference in actin and myosin content, regardless of genotype, although KCl-induced force tended to be lower in homozygous and higher in heterozygous mutants than in WTs. Conversely, in skinned fibers, myosin content and maximal force were significantly lower in Cald1-/- than in WTs. In KO abdominal aortas, resting and U46619 elicited force were lower than in WTs. Our results are consistent with the notion that CaD impacts smooth muscle function dually by (1) acting as a molecular brake on contraction and (2) maintaining the structural integrity of the contractile machinery. Most importantly, CaD is essential for resolution of the physiological umbilical hernia and ventral body wall closure.

Implications of comparative ventral body wall histology on selection of abdominal surgical approach and closure in 12 species of fish.

A ventral midline surgical approach for fish celiotomy is commonly performed in veterinary clinical medicine and research, although the relevant ventral body wall anatomy of many fish species is not well documented. Histological evaluation of tissue samples from the ventral body wall of 12 fish species was performed to provide a reference for surgical approach and closure decisions. The width between muscle bundles running parallel to the long axis and total thickness of tissue layers varied among species. An appreciable space between longitudinal muscles of the ventral body wall and a lack of muscle, vessels and nerves on midline in all species examined supports recommendations of ventral midline incisions to spare important structures. Dense connective tissue consistent with an aponeurosis between musculature along the ventral body wall was not observed in any species evaluated. Connective tissue was concentrated within the dermis of all species evaluated, with an additional layer of collagen along the coelomic membrane in Russian sturgeon Acipenser gueldenstaedtii, koi Cyprinus carpio, goldfish Carassius auratus, black drum Pogonias cromis, black seabass Centropristis striata, tomtate Haemulon aurolineatum and scup Stenotomus caprinus. A sufficiently wide space on ventral midline for practical targeting during the surgical approach is present in A. gueldenstaedtii, C. carpio, striped bass Morone saxatilis, H. aurolineatum, P. cromis, rainbow trout Oncorhynchus mykiss and brown trout Salmo trutta. Sand perch Diplectrum formosum, C. auratus, S. caprinus, grey triggerfish Balistes capriscus and black sea bass Centropristis striata have a negligible space between longitudinal muscles on midline. The variation in ventral body wall structure observed in this study helps inform surgical decision making for celiotomy incision and closure in these species.

Giant Omphalocele: 23 Patients; Three Different Approaches

Objective: Omphalocele is the ventral body wall maldevelopment. Early surgical interventions in the treatment of giant omphaloceles (GO) can increase morbidity and mortality. In this study, it was aimed to compare the advantages and disadvantages of primary closure, silo and vacuum assisted closure (VAC) methods used in omphalocele treatment. Materials and Methods: Three different treatment methods applied to 23 patients with giant omphalosis who were treated in our clinic between 2005 and 2020 were compared. Silo method was used in the treatment of 14 patients. Primary repair was performed in 7 patients. Mesh was used in 2 patients who underwent primary repair. The VAC was preferred for 2 patients. Treatments were discussed in terms of hospital stay, epithelization time, infections, and post-discharge problems. Results: Sepsis, ileus, gastroesophageal reflux and respiratory system problems were encountered after the silo method and primary repair, which are the classical methods of omphalocele treatment. VAC in technique, epithelization and healing were faster and only bilateral inguinal hernia developed as a complication. Conclusion: Minimizing complications with its effects that increase epithelization and prevent infection, VAC when other methods are considered in the treatment of giant omphalocele, it should be the first method that comes to mind.

Sonographic Evaluation of Coprostatic Impaction with Sand and Ingesta in Draft Equids

Background: Impaction of colons is a major cause of deaths in equines; therefore the objective of the current study was to perform the detailed ultrasonographic examination of equids suffering from abdominal discomfort and to identify which measurable parameters were important in reaching a diagnosis of small intestinal abnormality and determining treatment options. Methods: In this study twenty five equids (age 10-13 years) with history of cessation of defecation ranging from 2-4 days were subjected to sonography. Result: The impaction of left ventral colon in all animals was imaged as hyperechoic intraluminal structure casting a strong acoustic shadow with loss of normal sacculations, edema, increase in wall thickness and absence of peristaltic activity. Findings giving an indication of sand colic were the flattening of left ventral colon wall against the ventral body wall with loss of normal sacculations, peristaltic activity, presence of small pinpoint hyperechoic structures on the mucosal surface seen casting small acoustic shadows and reverberation artifacts in different directions were highly suggestive of sand impaction. In all animals the loops of small intestine were observed in transverse as well as longitudinal sections as hypermotile distended with fluidy ingesta and hyperechoic feed particles swirling inside that fluidly ingesta. The presence of dilated multiple loops of intestine in a single scanning area was a consistent feature of left ventral colon impaction. Hence detailed ultrasonographic examination was useful to delineate normal and abnormal conditions and to distinguish between true and false colic which provided an important diagnostic lead in management of affections of left ventral colon.

Teratogenesis in the chick embryo following post-gastrulation exposure to Y-27632 -effect of Y-27632 on embryonic development

The pyridine derivative Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in numerous developmental processes during embryogenesis, primarily by controlling actin-cytoskeleton assembly and cell contractility. Somite formation requires rearrangement of the cytoskeleton and assists in major morphological mechanisms, including ventral body wall formation. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos leading to ventral body wall defects (VBWD) at later stages of development. The aim of this study was to investigate the effect of Y-27632 on somite development in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Following administration, abnormality rates were assessed. In treatment groups, embryos showed a kinked longitudinal body axis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated cofilin-2. Histology, Lysotracker studies and RT-PCR demonstrated increased cell death in somites, the neural tube and the ectoderm. RT-PCR and Western blot of factors known to be involved during somitogenesis revealed reduced expression in the treatment group compared to controls. We hypothesize that administration of Y-27632 disrupts somite development causing axial kinking and embryo malformation, which may lead to VBWD.

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans.

The changes in the plasma membrane localization of the epidermal growth factor receptor (EGFR) and its downstream effector RAS have been implicated in several diseases including cancer. The free-living nematode C. elegans possesses an evolutionary and functionally conserved EGFR-RAS-ERK MAP signal cascade which is central for the development of the vulva. Gain of function mutations in RAS homolog LET-60 and EGFR homolog LET-23 induce the generation of visible nonfunctional ectopic pseudovulva along the ventral body wall of these worms. Previously, the multivulval (Muv) phenotype in these worms has been shown to be inhibited by small chemical molecules. Here we describe a protocol for using the worm in a liquid-based assay to identify inhibitors that abolish the activities of EGFR and RAS proteins. Using this assay, we show R-fendiline, an indirect inhibitor of K-RAS, suppresses the Muv phenotype expressed in the let-60(n1046) and let-23(sa62) mutant worms. The assay is simple, inexpensive, is not time consuming to setup, and can be used as an initial platform for the discovery of anticancer therapeutics.

<i>Elpidia soyoae</i>, a New Species of Deep-sea Holothurian (Echinodermata) from the Japan Trench Area

A new species of holothurian, Elpidia soyoae sp. nov., is described from the Japan Trench area, at depths of 3570–4145 m. It is distinguished from its congeners in having: four or five paired papillae and unpaired papillae present along entire dorsal radii (four to seven papillae on each radius), with wide separation between second and third paired papillae; maximum length of Elpidia-type ossicles in dorsal body wall exceeds 1000 µm; axis diameter of dorsal Elpidia-type ossicles less than 40 µm; tentacle Elpidia-type ossicles with arched axis and shortened, occasionally completely reduced arms and apophyses. Purple pigmentation spots composed of small purple particles on both dorsal and ventral body wall. This is the second species of Elpidia Théel, 1876 from Japanese abyssal depths. The diagnosis of the genus Elpidia is modified to distinguish from all other elpidiid genera. A morphological comparison of the species of the slender axis group of genus Elpidia, and partial mitochondrial cytochrome c oxidase subunit I (COI) gene sequences of type specimens are provided.

In‐frame Genetic Disruption of SPECC1L Microtubule‐Interaction Domain Causes Embryonic Tissue Movement and Fusion Defects

Movement and fusion events are critical during embryonic development; defects in these events lead to common birth anomalies. For example, failure of neural tube, secondary palate and ventral body wall closure leads to exencephaly, cleft palate, and omphalocele, respectively. Autosomal‐dominant SPECC1L mutations have been identified in patients with syndromic malformations, including hypertelorism, cleft palate and omphalocele. These mutations cluster in the second coiled‐coil (CCD2) and calponin homology (CHD) domains, which interact with microtubule and actin, respectively. To study SPECC1L function in mice, we first generated genomic deletions that resulted in out‐of‐frame truncations. Homozygous mutants for these truncations, including those lacking CCD2 and CHD, died shortly after birth without cleft palate or omphalocele. We then generated a series of targeted in‐frame deletions in CCD2, homozygotes for which also exhibited perinatal lethality but now with ~50% exencephaly, ~50% cleft palate, and ~50% omphalocele. While the omphalocele phenotype segregated equally with the other two phenotypes, exencephaly and cleft palate were never observed in the same embryo, suggesting antagonistic tissue mechanics between neural tube and palate closure. Consistently, we found that the oral cavity was narrower in mutant embryos with exencephaly, allowing for the palatal shelves to close eventually. We have shown previously that SPECC1L deficiency leads to impaired cell speed and directionality. We now show that subcellular SPECC1L‐ΔCCD2 protein distribution was abnormal, accumulating asymmetrically and associating almost exclusively with filamentous actin. Thus, loss of SPECC1L interaction with microtubules – while maintaining actin association – was more detrimental to cell and tissue movement than loss of SPECC1L protein entirely. Taken together, our results showed that in‐frame perturbations of CCD2 in SPECC1L protein specifically affect embryonic closure of several tissues, suggesting that human SPECC1L CCD2 missense mutations are gain‐of‐function. Our data also revealed a novel role for SPECC1L cross‐linking of actin and microtubule cytoskeletons in embryonic tissue movement and fusion events.Support or Funding InformationThis project was supported in part by the National Institutes of Health grants DE026172 (I.S.). Core support and pilot funding was also provided by National Institutes of Health Center of Biomedical Research Excellence (COBRE) grant (P20 GM104936), Kansas IDeA Network for Biomedical Research Excellence (INBRE) grant (P20 GM103418), and Kansas Intellectual and Developmental Disabilities Research Center (IDDRC) grant (P30 HD 002528).

Relationship between rectal abdominis muscle position and physiological umbilical herniation and return: A morphological and morphometric study.

The herniation of the intestinal loop (IL) in the extraembryonic coelom and its return to abdominal cavity is in parallel with the formation of the rectal abdominis muscle (RAM). Using high-resolution magnetic resonance imaging data of human fetuses (n = 19, CRL22-69 mm; stored at Kyoto Collection), this study aimed to analyze the relationship between the development of RAM and phase of IL herniation. The RAM runs at the lateral part of the abdominal wall in the small samples in the herniation phase. The position was shifted to the midline area in the larger samples in the herniation phase. According to fetal growth, the caudal ends of the muscles extended along the umbilical ring towards the pubis, though the caudal part of the RAMs were thin and faint in most of the samples. Length measurements related with the growth of the abdominal wall including RAM and abdominal circumference showed positive correlation with fetal growth. On the contrary, diastasis of RAMs and the width and area of the umbilical ring were almost constant according to fetal growth. Such morphometric value showed no obvious changes regardless of the phases of herniation. The ratio of the width and diastasis of the RAMs to the circumference was decreased, indicating that the closure of the ventral body wall was influenced by growth differences. The present data indicate that the formation of the abdominal wall including RAM is independent of the phase of IL herniation, whether in the extraembryonic coelom or in the abdominal cavity.

The Fgf8 subfamily (Fgf8, Fgf17 and Fgf18) is required for closure of the embryonic ventral body wall.

ABSTRACTThe closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are extruded. By refining where and when these genes are required using different Cre lines, we show that Fgf8 and Fgf17 are required in the presomitic mesoderm, whereas Fgf18 is required in the somites. This study identifies complex and multifactorial origins of ventral wall defects and has important implications for understanding their origins during embryonic development.

Fetal Autopsy Showing Two Ventral Body Wall Defects: An Unusual Presentation

Thoracoschisis and gastroschisis are types of ventral body wall defects. Usually thoracoabdominoschisis presents as a continuous defect. Here the authors present the case of autopsy of 18 weeks old fetus with two well-separated ventral body wall defects. Thoracoschisis was a right lateral thoracic wall defect while gastroschisis, a midline infraumblical abdominal wall defect. Through the right lateral thoracic wall parts of two organs appeared to be protruding. On dissection, 8th and 9th ribs with the liver and the lower lobe of the right lung were herniating outside the body. The right lung was haemorrhagic. Various embryological theories on ventral body wall defects have been discussed in view of the present case.

Holothuria (Mertensiothuria) viridiaurantia sp. nov. (Holothuriida, Holothuriidae), a new sea cucumber from the Eastern Pacific Ocean revealed by morphology and DNA barcoding.

Holothuria (Mertensiothuria) viridiaurantiasp. nov. is described based on specimens from rocky reefs of northern Chocó in the Colombian Pacific Ocean; however, it also occurs along the Eastern Pacific Ocean from Mexico and Panama. Although specimens from Mexico and Panama were previously identified as Holothuria (Mertensiothuria) hilla Lesson, 1830 the new species is easily distinguished morphologically and via mtDNA. In terms of morphology, the species can be identified by its olive-green background and white-orange papillae and tentacles, larger tentacles with deep indentations and also by larger buttons on the dorsal and ventral body wall, papillae and tube feet; large, thick and rough tentacle rods, and the absence of ossicles in the longitudinal muscles. The new species is included in the subgenus Mertensiothuria considering molecular evidence.

BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis.

BMP7/BMP2 or BMP7/BMP4 heterodimers are more active than homodimers in vitro, but it is not known whether these heterodimers signal in vivo. To test this, we generated knock in mice carrying a mutation (Bmp7R-GFlag) that prevents proteolytic activation of the dimerized BMP7 precursor protein. This mutation eliminates the function of BMP7 homodimers and all other BMPs that normally heterodimerize with BMP7. While Bmp7 null homozygotes are live born, Bmp7R-GFlag homozygotes are embryonic lethal and have broadly reduced BMP activity. Furthermore, compound heterozygotes carrying the Bmp7R-G allele together with a null allele of Bmp2 or Bmp4 die during embryogenesis with defects in ventral body wall closure and/or the heart. Co-immunoprecipitation assays confirm that endogenous BMP4/7 heterodimers exist. Thus, BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian development, which may explain why mutations in either Bmp4 or Bmp7 lead to a similar spectrum of congenital defects in humans.

Morphological evidence of neurotoxic effects in chicken embryos after exposure to perfluorooctanoic acid (PFOA) and inorganic cadmium

Perfluorooctanoic acid (PFOA) and cadmium (Cd) are persistent environmental pollutants, bioaccumulative, and capable of crossing the placental barrier. There is evidence of developmental toxicity induced by PFOA and Cd, but their effects on early development are still poorly understood. In the present study, chicken embryos were exposed to PFOA, Cd, and a mixture of PFOA + Cd from blastula stage up to 72 h of incubation. Embryo mortality and morphology were assessed. PFOA and Cd exposure increased mortality and induced malformations, mainly in the cephalic region, the neural tube, and the ventral body wall. After mixed exposure the effect was observed mostly in the neural tube and the cephalic region. However, the mechanism remains unknown. Because of the resemblance between human and chick development, it was possible to correlate the observed alterations in chickens with known human congenital malformations. Therefore, PFOA and Cd are neurotoxic to chicken embryos inducing morphological abnormalities and are possibly neurotoxic to human embryos.

Database for Gene Variants and Metabolic Networks Implicated in Familial Gastroschisis

Gastroschisis is one of the most prevalent human birth defects concerning the ventral body wall development. Recent research has given a better understanding of gastroschisis pathogenesis through the identification of multiple novel pathogenetic pathways implicated in ventral body wall closure. Deciphering the underlying genetic factors segregating among familial gastroschisis allows better detection of novel susceptibility variants than the screening of pooled unrelated cases and controls, whereas bioinformatic-aided analysis can help to address new insights into human biology and molecular mechanisms involved in gastroschisis. Technological advances in DNA sequencing (Next Generation Sequencing), computing power, and machine learning techniques provide opportunities to the scientific communities to assess significant gaps in research and clinical practice. Thus, in an effort to study the role of gene variation in gastroschisis, we employed whole exome sequencing in a Mexican family with recurrence for gastroschisis. Stringent bioinformatic analyses were implemented to identify and predict pathogenetic networks comprised of potential gastroschisis predispositions. This is the first database for gene variants and metabolic networks implicated in familial gastroschisis. The dataset provides information on gastroschisis annotated genes, gene variants, and metabolic networks and constitutes a useful source to enhance further investigations in gastroschisis.

Bioinformatic Analysis of Gene Variants from Gastroschisis Recurrence Identifies Multiple Novel Pathogenetic Pathways: Implication for the Closure of the Ventral Body Wall.

We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9, and FGFR4. SVS–PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B, SLC9A3, ITGA2, AOX1, and ALPP, including a recessive model in UGT1A7, UGT1A6, PER2, PTPRD, and UGT1A3. A heterozygous compound model was observed in CDYL, KDM5A, RASGRP1, MYBPC2, PDE4DIP, F5, OBSCN, and UGT1A. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.

Colopexy dehiscence preceding an episode of large colon volvulus, followed by repeat colopexy, in three Thoroughbred broodmares

SummaryThree Thoroughbred mares that had undergone previous colopexy following surgical correction of a large colon volvulus presented for colic signs unresponsive to medical management. Exploratory laparotomy was elected and a midline celiotomy was performed in the caudal aspect of the ventral abdomen in each mare. Examination of the cranial abdomen revealed the large colon was not adhered to the ventral body wall, indicating dehiscence of the previous colopexy. Further examination of the abdomen in each mare revealed a 360‐degree large colon volvulus. The previous colopexy site appeared as a linear haemorrhagic area of fibrosis in one mare and a pale area of fibrosis in two mares. The large colon volvulus was corrected and a second colopexy was then performed using the same technique as the first colopexy – by incorporating 10–12 cm of the lateral free band of the left ventral colon into the midline linea alba closure using number 3 polyglactin 910 (Vicryl®). The mares each recovered uneventfully from anaesthesia and were discharged 2–10 days later. Two of the mares are still alive at the time of manuscript submission, 475 and 789 days post‐operatively. The third mare survived 4 years post‐operatively, following which she was lost to follow‐up. Data available from our clinic indicate an incidence rate of 0.79% for colopexy dehiscence followed by a repeat episode of large colon volvulus. This phenomenon should be considered as a differential diagnosis when a mare that previously underwent a colopexy presents with severe signs of colic.