Biomaterial Database

Failure of neural tube closure in the loop-tail (Lp) mutant mouse: analysis of the embryonic mechanism. 1997

D Gerrelli, and A J Copp

Neural Development Unit, University College London, UK.

Loop-tail (Lp) is unique among mouse mutants in failing to initiate neural tube closure at the cervical/hindbrain boundary (so-called 'Closure 1'), at the 5-7 somite stage. Lp/Lp embryos go on to develop a malformation that closely resembles cranio-rachischisis, the most severe neural tube defect found in humans. We investigated several possible embryological mechanisms that may underlie this failure of neural tube closure in Lp. The genotypes of Lp/Lp, Lp/+ and +/+ embryos from mixed litters were identified using the polymerase chain reaction to amplify a polymorphic microsatellite sequence that is very closely linked to Lp. At post-neurulation stages of development, Lp/Lp embryos have a shortened body axis, which could suggest a defect of axial elongation as the primary anomaly in Lp. However, we found that axial elongation is normal in Lp homozygotes prior to the stage of defective Closure 1, indicating that the shortened body axis of later embryos is a secondary effect of the neurulation anomaly, or an independent effect of the Lp mutation. Some workers have reported cell proliferation rates to be abnormal in later stage Lp/Lp embryos. We observed variations in [3H]thymidine labelling index, and mitotic index, between embryonic tissues, and between embryos at different somite stages. However, Lp/Lp, Lp/+ and +/+ embryos had closely similar cell proliferation parameters, arguing against a mechanism based on faulty embryonic growth. Thirdly, we tested the hypothesis that the defect in loop-tail results from an inability of the neural folds to become apposed, specifically at the site of Closure 1. By tying a silk suture around the embryonic axis, at the future site of Closure 1, we were able to effect convergence of the neural folds at this site. Neural fold closure failed to progress along the body axis in sutured Lp/Lp embryos, however, in contrast to operated Lp/+ and +/+ embryos which exhibited normal progression of neural tube closure. The embryonic defect in loop-tail appears, therefore, to involve either a general inability of the spinal neural folds to become apposed along the spinal region, or a defect in the process of neural fold fusion.

UI	MeSH Term	Description	Entries
D008808	Mice, Inbred CBA	An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH.	Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008818	Mice, Neurologic Mutants	Mice which carry mutant genes for neurologic defects or abnormalities.	Lurcher Mice,Nervous Mice,Reeler Mice,Staggerer Mice,Weaver Mice,Chakragati Mice,Chakragati Mouse,Lurcher Mouse,Mice, Neurological Mutants,Mouse, Neurologic Mutant,Mouse, Neurological Mutant,Nervous Mouse,Neurologic Mutant Mice,Neurological Mutant Mouse,Reeler Mouse,Staggerer Mouse,Weaver Mouse,ckr Mutant Mice,Mice, Chakragati,Mice, Lurcher,Mice, Nervous,Mice, Neurologic Mutant,Mice, Reeler,Mice, Staggerer,Mice, Weaver,Mice, ckr Mutant,Mouse, Chakragati,Mouse, Lurcher,Mouse, Nervous,Mouse, Reeler,Mouse, Staggerer,Mouse, Weaver,Mutant Mice, Neurologic,Mutant Mice, ckr,Mutant Mouse, Neurologic,Neurologic Mutant Mouse
D009436	Neural Tube Defects	Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)	Craniorachischisis,Developmental Defects, Neural Tube,Diastematomyelia,Exencephaly,Neurenteric Cyst,Spinal Cord Myelodysplasia,Tethered Cord Syndrome,Acrania,Developmental Neural Tube Defects,Iniencephaly,Neural Tube Developmental Defects,Neuroenteric Cyst,Occult Spinal Dysraphism,Occult Spinal Dysraphism Sequence,Tethered Spinal Cord Syndrome,Acranias,Craniorachischises,Cyst, Neurenteric,Cyst, Neuroenteric,Cysts, Neurenteric,Cysts, Neuroenteric,Defect, Neural Tube,Defects, Neural Tube,Diastematomyelias,Dysraphism, Occult Spinal,Dysraphisms, Occult Spinal,Exencephalies,Iniencephalies,Myelodysplasia, Spinal Cord,Myelodysplasias, Spinal Cord,Neural Tube Defect,Neurenteric Cysts,Neuroenteric Cysts,Occult Spinal Dysraphisms,Spinal Cord Myelodysplasias,Spinal Dysraphism, Occult,Spinal Dysraphisms, Occult,Tethered Cord Syndromes
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D005260	Female		Females
D005314	Embryonic and Fetal Development	Morphological and physiological development of EMBRYOS or FETUSES.	Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal
D005865	Gestational Age	The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination.	Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013536	Suture Techniques	Techniques for securing together the edges of a wound, with loops of thread or similar materials (SUTURES).	Suture Technics,Suture Technic,Suture Technique,Technic, Suture,Technics, Suture,Technique, Suture,Techniques, Suture
D046508	Culture Techniques	Methods of maintaining or growing biological materials in controlled laboratory conditions. These include the cultures of CELLS; TISSUES; organs; or embryo in vitro. Both animal and plant tissues may be cultured by a variety of methods. Cultures may derive from normal or abnormal tissues, and consist of a single cell type or mixed cell types.	Culture Technique,Technique, Culture,Techniques, Culture