Some Mice Feature 5th Pharyngeal Arch Arteries and Double-Lumen Aortic Arch Malformations

Geyer, Stefan H.; Weninger, Wolfgang J.

doi:10.1159/000330789

Cited by 26 publications

(23 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surface model of the great intrathoracic arteries on top of an original HREM section of a Pdzk1 -/- embryo. (Compare with 16). F. “Intramural bleeding in blood vessel wall” (arrowhead) in the descending aorta (da) of an Akap9 -/- embryo from the DMDD pilot study 8 .…”

Section: Tablementioning

confidence: 95%

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

Wilson¹,

Geyer²,

Reissig³

et al. 2017

Wellcome Open Res

Self Cite

View full text Add to dashboard Cite

Identifying genes that are essential for mouse embryonic Background: development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities.Here we present results gathered to date in the Deciphering the Methods: Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5.Virtually all mutant embryos show multiple abnormal phenotypes and Results: amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve.Overall, the most striking finding is that no matter how profound Conclusions: the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates.

show abstract

Section: Tablementioning

confidence: 95%

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

Wilson¹,

Geyer²,

Reissig³

et al. 2017

Wellcome Open Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have previously shown the efficacy of this imaging method for both qualitative and quantitative analysis of organogenesis in mouse embryos, providing as it does, the highest resolution 3D analysis of embryo morphology currently available (Bamforth et al, 2013; Dunlevy et al, 2010; Geyer and Weninger, 2012; Geyer et al, 2012; Geyer and Weninger, 2013; Mohun and Weninger, 2011; Pieles et al, 2007; Weninger et al, 2009). Using embryos from recessive embryonic and perinatal lethal lines produced as part of the UK contribution to the IKMC knockout programme, we have now assessed the nature, range and probable severity of the structural phenotypes, identified using HREM, and outline a simple screening protocol that enables HREM data to be reviewed in an efficient and timely manner.…”

Section: Introductionmentioning

confidence: 92%

Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy

Weninger

Geyer

Martineau³

et al. 2014

Disease Models &Amp; Mechanisms

Self Cite

View full text Add to dashboard Cite

The arrival of simple and reliable methods for 3D imaging of mouse embryos has opened the possibility of analysing normal and abnormal development in a far more systematic and comprehensive manner than has hitherto been possible. This will not only help to extend our understanding of normal tissue and organ development but, by applying the same approach to embryos from genetically modified mouse lines, such imaging studies could also transform our knowledge of gene function in embryogenesis and the aetiology of developmental disorders. The International Mouse Phenotyping Consortium is coordinating efforts to phenotype single gene knockouts covering the entire mouse genome, including characterising developmental defects for those knockout lines that prove to be embryonic lethal. Here, we present a pilot study of 34 such lines, utilising high-resolution episcopic microscopy (HREM) for comprehensive 2D and 3D imaging of homozygous null embryos and their wild-type littermates. We present a simple phenotyping protocol that has been developed to take advantage of the high-resolution images obtained by HREM and that can be used to score tissue and organ abnormalities in a reliable manner. Using this approach with embryos at embryonic day 14.5, we show the wide range of structural abnormalities that are likely to be detected in such studies and the variability in phenotypes between sibling homozygous null embryos.

show abstract

“…The fifth PAAs do not contribute to the mature aortic arch in mammals and whether the fifth PAA forms at all remains controversial (Bamforth et al, 2013;de Ruiter, Gittenberger-de Groot, Rammos, & Poelmann, 1989;Geyer & Weninger, 2012). The left and right third PAAs contribute to their respective carotid arteries (Hiruma et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Reduced maternal vitamin A status increases the incidence of normal aortic arch variants

Sugrue

Zohn

2019

Genesis

View full text Add to dashboard Cite

While common in the general population, the developmental origins of "normal" anatomic variants of the aortic arch remain unknown. Aortic arch development begins with the establishment of the second heart field (SHF) that contributes to the pharyngeal arch arteries (PAAs). The PAAs remodel during subsequent development to form the mature aortic arch and arch vessels. Retinoic acid signaling involving the biologically active metabolite of vitamin A, plays a key role in multiple steps of this process. Recent work from our laboratory indicates that the E3 ubiquitin ligase Hectd1 is required for full activation of retinoic acid signaling during cardiac development. Furthermore, our study suggested that mild alterations in retinoic acid signaling combined with reduced gene dosage of Hectd1, results in a benign aortic arch variant where the transverse aortic arch is shortened between the brachiocephalic and left common carotid arteries. These abnormalities are preceded by hypoplasia of the fourth PAA. To further explore this interaction, we investigate whether reduced maternal dietary vitamin A intake can similarly influence aortic arch development.Our findings indicate that the incidence of hypoplastic fourth PAAs, as well as the incidence of shortened transverse arch are increased with reduced maternal vitamin A intake during pregnancy. These studies provide new insights as to the developmental origins of these benign aortic arch variants. K E Y W O R D Saortic arch development, congenital heart defects, Hectd1, retinoic acid, vitamin A deficiency

show abstract

Some Mice Feature 5th Pharyngeal Arch Arteries and Double-Lumen Aortic Arch Malformations

Cited by 26 publications

References 75 publications

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy

Reduced maternal vitamin A status increases the incidence of normal aortic arch variants

Contact Info

Product

Resources

About