Prevention of neural tube defects in curly-tail mice by maternal administration of vitamin A

1982 ◽  
Vol 2 (4) ◽  
pp. 297-300 ◽  
Author(s):  
Mary J. Seller ◽  
Kathleen I. Perkins
Keyword(s):  
Vitamin A ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Curly Tail ◽  
Maternal Administration

Neural tube defects in curly-tail mice. II. Effect of maternal administration of vitamin A

1979 ◽  
Vol 206 (1162) ◽  
pp. 95-107 ◽  
Keyword(s):  
Vitamin A ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Neural Tube Closure ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Curly Tail ◽  
The Central Nervous System ◽  
Maternal Administration

Vitamin A, a known teratogen of the central nervous system, was administered in various doses, at the time of active neural tube closure, to pregnant curly-tail mice which have a genetic predisposition to neural tube defects (n. t. d. ), and to A Strong mice, which are not so predisposed. The curly-tail mice showed an enhanced susceptibility to the terato­genic effect of vitamin A given on day 8 of gestation, demonstrating a clear gene─environment interaction. There was a differential response by the two sexes. Females seemed to be more affected by the vitamin A than males. When vitamin A was administered on day 9, instead of day 8, of gestation, the incidence of n. t. d. decreased rather than increased. Furthermore, the number of mice affected by n. t. d. was markedly lower even than that found spontaneously in untreated curly-tail mice.

Genesis and prevention of spinal neural tube defects in the curly tail mutant mouse: involvement of retinoic acid and its nuclear receptors RAR-beta and RAR-gamma

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 681-691
Author(s):  
W.H. Chen ◽  
G.M. Morriss-Kay ◽  
A.J. Copp
Keyword(s):  
Retinoic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
In Situ Hybridisation ◽  
Tail Bud ◽  
Retinoic Acid Signalling ◽  
All Trans Retinoic Acid ◽  
Posterior Neuropore ◽  
Computerised Image Analysis ◽  
Curly Tail

A role for all-trans-retinoic acid in spinal neurulation is suggested by: (1) the reciprocal domains of expression of the retinoic acid receptors RAR-beta and RAR-gamma in the region of the closed neural tube and open posterior neuropore, respectively, and (2) the preventive effect of maternally administered retinoic acid (5 mg/kg) on spinal neural tube defects in curly tail (ct/ct) mice. Using in situ hybridisation and computerised image analysis we show here that in ct/ct embryos, RAR-beta transcripts are deficient in the hindgut endoderm, a tissue whose proliferation rate is abnormal in the ct mutant, and RAR-gamma transcripts are deficient in the tail bud and posterior neuropore region. The degree of deficiency of RAR-gamma transcripts is correlated with the severity of delay of posterior neuropore closure. As early as 2 hours following RA treatment at 10 days 8 hours post coitum, i.e. well before any morphogenetic effects are detectable, RAR-beta expression is specifically upregulated in the hindgut endoderm, and the abnormal expression pattern of RAR-gamma is also altered. These results suggest that the spinal neural tube defects which characterise the curly tail phenotype may be due to interaction between the ct gene product and one or more aspects of the retinoic acid signalling pathway.

Neural tube development in mutant (curly tail) and normal mouse embryos: the timing of posterior neuropore closure in vivo and in vitro

Development ◽  
1982 ◽  
Vol 69 (1) ◽  
pp. 151-167
Author(s):  
A. J. Copp ◽  
M. J. Seller ◽  
P. E. Polani
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Mouse Embryos ◽  
Injection Technique ◽  
Posterior Neuropore ◽  
Curly Tail ◽  
Mechanisms Of Development ◽  
Delayed Closure

A dye-injection technique has been used to determine the developmental stage at which posterior neuropore (PNP) closure occurs in normal and mutant curly tail mouse embryos. In vivo, the majority of non-mutant embryos undergo PNP closure between 30 and 34 somites whereas approximately 50% of all mutant embryos show delayed closure, and around 20% maintain an open PNP even at advanced stages of development. A similar result has been found for embryos developing in vitro from the headfold stage. Later in development, 50–60% of mutant embryos in vivo develop tail flexion defects, and 15–20% lumbosacral myeloschisis. This supports the view that delayed PNP closure is the main developmental lesion leading to the appearance of caudal neural tube defects in curly tail mice. The neural tube is closed in the region of tail flexion defects, but it is locally overexpanded and abnormal in position. The significance of these observations is discussed in relation to possible mechanisms of development of lumbosacral and caudal neural tube defects. This paper constitutes the first demonstration of the development of a genetically induced malformation in vitro.

scholarly journals Reduced Glucose Consumption in the Curly Tail Mouse Does Not Initiate the Pathogenesis Leading to Spinal Neural Tube Defects

1998 ◽  
Vol 128 (10) ◽  
pp. 1819-1828 ◽  
Author(s):  
Marian C. E. Peeters ◽  
Jan L.M.C. Geelen ◽  
Johan W. M. Hekking ◽  
Niels Chavannes ◽  
Joep P. M. Geraedts ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Glucose Consumption ◽  
Curly Tail

A cell-type-specific abnormality of cell proliferation in mutant (curly tail) mouse embryos developing spinal neural tube defects

Development ◽  
1988 ◽  
Vol 104 (2) ◽  
pp. 285-295 ◽  
Author(s):  
A.J. Copp ◽  
F.A. Brook ◽  
H.J. Roberts
Keyword(s):  
Cell Proliferation ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Posterior Neuropore ◽  
Curly Tail ◽  
A Cell ◽  
Notochord Cells ◽  
Cell Type Specific ◽  
Reduced Rate ◽  
Gut Endoderm

The mouse mutant curly tail (ct) provides a model system for studies of neurulation mechanisms. 60% of ct/ct embryos develop spinal neural tube defects (NTD) as a result of delayed neurulation at the posterior neuropore whereas the remaining 40% of embryos develop normally. In order to investigate the role of cell proliferation during mouse neurulation, cell cycle parameters were studied in curly tail embryos developing spinal NTD and in their normally developing litter-mates. Measurements were made of mitotic index, median length of S-phase and percent reduction of labelling index during a [3H]thymidine pulse-chase experiment. These independent measures of cell proliferation rate indicate a reduced rate of proliferation of gut endoderm and notochord cells in the neuropore region of embryos developing spinal NTD compared with normally developing controls. The incidence of cell death and the relative frequency of mitotic spindle orientations does not differ consistently between normal and abnormal embryos. These results suggest a mechanism of spinal NTD pathogenesis in curly tail embryos based on failure of normal cell proliferation in gut endoderm and notochord.

The curly-tail (ct) mouse, an animal model of neural tube defects, displays altered homocysteine metabolism without folate responsiveness or a defect in Mthfr

2002 ◽  
Vol 76 (4) ◽  
pp. 297-304 ◽  
Author(s):  
Pamela Tran ◽  
Francois Hiou-Tim ◽  
Phyllis Frosst ◽  
Suzanne Lussier-Cacan ◽  
Pamela Bagley ◽  
...  
Keyword(s):  
Animal Model ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Curly Tail

Relationship between timing of posterior neuropore closure and development of spinal neural tube defects in mutant (curly tail) and normal mouse embryos in culture

Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 39-54
Author(s):  
Andrew J. Copp
Keyword(s):  
Causal Relationship ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Predisposition ◽  
Normal Mouse ◽  
Mouse Embryos ◽  
Posterior Neuropore ◽  
Curly Tail ◽  
Genetically Determined ◽  
The Relationship

The relationship between timing of closure of the posterior neuropore (PNP) and development of spinal neural tube defects (NTD) has been studied in individual mutant curly tail mouse embryos maintained in culture. Moderate delay in PNP closure results in development of tail flexion defects whereas extreme delay of PNP closure is associated with development of open NTD. Experimental enlargement of the PNP at the stage of 25 to 29 somites leads to delayed PNP closure and development of tail flexion defects in 36 % and 38 % respectively of non-mutant A/Strong embryos. In curly tail embryos, the effect of experimental enlargement of the PNP summates with the genetic predisposition to produce an increased incidence of spinal NTD among which open defects are proportionately more common. These results indicate that a causal relationship exists between delay in PNP closure and development of spinal NTD in mouse embryos. The method described for distinguishing between prospective normal and abnormal curly tail embryos at a stage prior to the appearance of malformations provides an opportunity to study the morphogenetic processes that precede the development of genetically determined spinal NTD.

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