Biotech Articles
Publish Your Research Online
Get Recognition - International Audience

Request for an Author Account   |   Login   |   Submit Article
 
 
HOME FAQ TOP AUTHORS FORUMS PUBLISH ARTICLE
 
 

Animal Model for Neural Tube Defects

BY: Geetanjali Murari | Category: Healthcare | Submitted: 2014-11-25 09:37:01
       Author Photo
Article Summary: "This article deals with the significant animal model used in research for studying neural tube defects. The best animal models are illustrated here..."


Share with Facebook Share with Linkedin Share with Twitter Share with Pinterest Email this article
     


Animal Model for Neural Tube Defects

Neural Tube Defects (NTDs): This is one of the most common severely disabling birth defects affecting approximately 1 in every 2,000 births.

• This is due to the failure of closure of neural tube which is observed during 4th week of embryogenesis.

• Anencephaly and spina bifida are the two most common neural tube defects.
    → Anencephaly- rostral part of the neural tube fails to develop into brain. They have brain stem which controls the reflexes like breathing.
    → Spina bifida: also known as "Split Spine". A bulge is seen in the lumbar-sacral region of the spinal cord.

Types of Spina Bifida: There are 3 types of spina bifida depending upon their severity-

(i) Myelomeningocele- this is considered to be the most severe form of the disease. The neural tube fails to fuse and protrude has been seen in the spinal cord. Severe nerve damage and major disabilities is experienced in this case.

(ii) Meningocele- A bulge in the lumbar-sacral region is seen in the spinal cord with minor disabilities and no nerve damage.

(iii) Spina Bifida Occulta- This is the least severe form of the disease. This is also known as hidden spina bifida as it is not even noticed through naked eyes. This is harmless without any nerve damage.

Causes

The causative factors of the disease are:

(i) Administration of the antiepileptic drug (valproic acid) during the first trimester of pregnancy could result in spina bifida.

(ii) Folic acid deficiencies during or before the pregnancy.

(iii) Folate Metabolism Pathway is suspected to be a major contributor.

Symptoms

The disease results in major disabilities like,

a) Paralysis, difficulty in movement.

b) Incontinence of urine and feces.

c) Abnormalities seen in the hips, knees, and feet.

d) Hydrocephalus- enhanced pressure of cerebrospinal fluid resulting in the swelling of brain.

Animal models for neural tube defects:

Spina Bifida is naturally found in dogs and cats. Research involving lambs showed it to be an autosomal recessive trait. Rats and mouse are generally used for studying the disease.

Mouse model:

Mouse is considered to be the perfect model for studying the underlying causes of NTDs. Mice models not only allow for identification of the genes required for neurulation, but they also provide tractable systems for uncovering the developmental, pathological and molecular mechanisms underlying NTDs. In addition to this, mouse models are essential for understanding the mechanisms of gene-environment and gene-gene interactions that contribute to the multifactorial inheritance of NTDs. These models also aid in the development of therapeutic approaches for the disease.

Sprague drawley rat model:

In this model, pregnant Sprague-Dawley rats weighing 180g were injected subcutaneously with 1% trypan blue on 7-8 day of gestational period to produce embryos with spina bifida or anencephaly. The control rats were given vehicle only. The scanning microscopic examination of 9-10 day old embryos revealed no morphologic differences between controls and subjects. Subsequent gestational days showed closure of neural tubes in controls but progressive opening of neural tubes in both the rostral and caudal regions were found in the diseased models. Growth of the dysmorphic neural tube region with subsequent spontaneous necrosis late in gestation resulted in the mature malformations of anencephaly and spina bifida. This study emphasizes the similarities in the developmental stages of spina bifida and anencephaly (Smith M.T, 1989).



Curly tail mouse model:

A mutation on mouse chromosome 4 positioned at 69 cm produces this model. The curly tail mutation produces variable percentage of curly tail mice even when homozygotes are mated together. This mouse has a curl in the proximal region of the tail and a lumbosacral spina bifida. Three manifestations seen in this model include exencephaly (outgrowth in the forebrain region), lumbosacral spina bifida and curled tail. The mouse model is fertile and tends to live longer.
The curly tail mutant mouse is an appropriate model for NTDs. The ct gene has variable expression and is incompletely penetrant with homozygotes developing exencephaly (around 3% of embryos), spina bifida aperta (10%) and a curled tail (50%). The curled tail phenotype is often associated with lumbosacral spina bifida in which the spinal cord and vertebral canal are both protruding outside. Spina bifida in the curly tail mouse arises from failure of primary neurulation curly tail morphology id due to the failure of secondary neurulation.

In humans, the neural tube defects involve multiple interacting genes and environmental factors and are considered to be multifactorial. Hence, analysiyng a single mouse mutant is not enough and can't be extrapolated in humans (Henny W.M et al., 2001).

Treatment:

• Surgery shortly after birth
• Folate supplementation helps prevent the defect through amino acid synthesis and reducing homocysteine levels
• About 90% of babies born with Spina Bifida live a longer life , about 80 percent have normal intelligence and about 75 percent play sports.

References:

• Smith M.T. Neonatal Animal Models: Experimental Anencephaly and Similarities to Spina Bifida. Int journal of Toxicology, 2014
• Nau H, Hauck RS, Ehlers K. Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacol Toxicol.1991 Nov;69(5)
• Juriloff D.M, Harris M.J. Mouse models for neural tube closure defects. Human Molecular Genetics, 2000; 9(6), 993-1000
• Henny W.M, Andrew J. Copp. Curly tail: a 50 year history of the mouse spina bifida model. Anat Embryol, 2001;203(4), 225-237

About Author / Additional Info:
I am currently doing my M.Phil in Neurosciences from NIMHANS (Bangalore)

Search this site & forums
Share this article with friends:



Share with Facebook Share with Linkedin Share with Twitter Share with Pinterest Email this article

More Social Bookmarks (Digg etc..)


Comments on this article: (0 comments so far)

Comment By Comment

Leave a Comment   |   Article Views: 2099



Additional Articles:

•   Naltrexone Drug in Treatment For Alcohol Dependence

•   Enzyme Immobilization - Methods and Applications

•   GABA Shunt: Biosynthesis and Metabolic Role in Plants

•   Biotechnology for Carrot Improvement




Latest Articles in "Healthcare" category:
•   Health Care and WHO

•   Current Scenario Of Gene Therapy

•   Targeted Cancer Therapy

•   Custom Made Medicine - Pharmacogenomics

•   Nanotechnology and its Application in Medicine - What are Nanoparticles?

•   Red Biotechnology and Cure of Tuberculosis

•   Patho-Biotechnology: Solution to Fight Antibiotic Resistance Bacteria?

•   A Baby Please With a Cheek Dimple...

•   Ribonucleic Acid Interference

•   Biomarker in Cancer Prognosis, Detection and Treatment

•   Adjuvant Therapy For Treating Cancer

•   DNA Microarray and Protein Microarray

•   DNA Vaccine: Vaccine of Next Generation

•   Cancer Immunotherapy Using Monoclonal Antibodies

•   Vaccines to Treat Cancer!

•   Tumor Marker and Cancer Detection

•   Targeted Therapy and Cancer Treatment

•   Enzyme Linked Immunosorbent Assay : A Biotechnology Technique

•   Lycopene as Anti-cancer Agent



Important Disclaimer: All articles on this website are for general information only and is not a professional or experts advice. We do not own any responsibility for correctness or authenticity of the information presented in this article, or any loss or injury resulting from it. We do not endorse these articles, we are neither affiliated with the authors of these articles nor responsible for their content. Please see our disclaimer section for complete terms.
Page copy protected against web site content infringement by Copyscape
Copyright © 2010 biotecharticles.com - Do not copy articles from this website.

ARTICLE CATEGORIES :
Agriculture Bioinformatics Applications Biotech Products Biotech Research
Biology Careers College/Edu DNA Environmental Biotech
Genetics Healthcare Industry News Issues Nanotechnology
Others Stem Cells Press Release Toxicology  


  |   Disclaimer/Privacy/TOS   |   Submission Guidelines   |   Contact Us