Comparison of inherited neural tube defects in companion animals and livestock

Abstract

Neural tube defects (NTDs) are congenital malformations resulting from the improper or incomplete closure of the neural tube during embryonic development. A number of similar malformations of the protective coverings surrounding the central nervous system are also often included under this umbrella term, which may not strictly fit this definition. A range of NTD phenotypes exist and have been reported in humans and a wide range of domestic and livestock species. In the veterinary literature, these include cases of anencephaly, encephalocele, dermoid sinus, spina bifida, and craniorachischisis. While environmental factors have a role, genetic predisposition may account for a significant part of the risk of NTDs in these animal cases. Studies of laboratory model species (fish, birds, amphibians, and rodents) have been instrumental in improving our understanding of the neurulation process. In mice, over 200 genes that may be involved in this process have been identified and variant phenotypes investigated. Like laboratory mouse models, domestic animals and livestock species display a wide range of NTD phenotypes. They remain, however, a largely underutilized population and could complement already established laboratory models. Here we review reports of NTDs in companion animals and livestock, and compare these to other animal species and human cases. We aim to highlight the potential of nonlaboratory animal models for mutation discovery as well as general insights into the mechanisms of neurulation and the development of NTDs.

Pentalogy of Cantrell in Two Neonate Littermate Puppies: A Spontaneous Animal Model Suggesting Familial Inheritance

“…Further, genomics and gene sequencing were not within the scope of this publication, though tissues have been retained for future investigations. This is specifically important, as a companion and other domestic animals have been revealed to be essential models for understanding pathogenesis and genetics in inherited developmental anomalies of dorsal midline closure defects [ 5 ].…”

“…An Australian epidemiologic study [ 2 ] estimated that 1.7% of stillbirth and early neonatal mortality in puppies are caused by congenital abnormalities ( n = 44 out of 2574 puppies). Given this, developmental anomalies in newborn companion animals provide an opportunity as spontaneous animal models for rare inherited human diseases and syndromes [ 3 , 4 , 5 ].…”

Exencephaly–Anencephaly Sequence Associated with Maxillary Brachygnathia, Spinal Defects, and Palatoschisis in a Male Domestic Cat

“…The embryonic development of the neural tube is a multistep process that is controlled by many genes, with more than 200 genes identified in mice that are involved in the formation of the neural tube [1]. Some of these genes are evolutionarily highly conserved, and their role in neurulation has been shown in multiple vertebrate animal models [4].…”

“…Neural tube defects (NTDs) are a group of severe congenital malformations of the nervous system caused by incorrect or incomplete closure of the neural tube during embryonic development [1]. There are two main ways in which the neural tube is formed from the neural plate during embryonic development: primary neurulation for the brain and most of the spinal cord, and secondary neurulation for the sacrum and tail bud [2,3].…”

“…In the veterinary literature, the main forms of NTDs reported other than anencephaly are encephalocele, craniorachischisis, dermoid sinus, and spina bifida [1]. These forms of NTDs are classified as cranial dysraphism (e.g., anencephaly, encephalocele, craniorachischisis) and as spinal dysraphism (e.g., spina bifida cystica, spina bifida occulta).…”