Neural tube defects in curly-tail mice. I. Incidence, expression and similarity to the human condition

Embury, Susan; Seller, Mary J.; Adinolfí, Matteo; Polani, P. E.

doi:10.1098/rspb.1979.0092

Cited by 59 publications

(9 citation statements)

References 10 publications

(8 reference statements)

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“…While the incidence of total spinal NTD did not vary between dams with straight or curly tails, spina bifida embryos were produced significantly more frequently by curly-tailed than by straight-tailed dams, and spina bifida embryos of curly-tailed dams were significantly more resistant to RA treatment than those of straight-tailed dams. This finding is reminiscent of the observation of Embury et al (1979) who found that matings between curly-tailed mice produce a higher incidence of total NTD than matings between straight-tailed mice. In contrast, Copp et al (1982) found no increase in penetrance of spinal NTD between the two types of matings.…”

Section: Penetrance Of Spina Bifida and Its Prevention By Ra Depend Osupporting

confidence: 54%

“…The curly-tail mutation (ct) is recessive with partial penetrance: Around 60% of homozygotes (ctlct) are affected (Gruneberg, 1954;Embury et al, 1979). There is also variable expressivity with the affected mice manifesting either an isolated tail flexion defect (a curled or kinked tail) or lumbosacral spina bifida together with a tail defect.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of spinal neural tube defects in the curly tail mouse mutant by a specific effect of retinoic acid

Chen

Morriss‐Kay

Copp

1994

Developmental Dynamics

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Curly tail mouse mutant embryos (ctlct) develop spinal neural tube defects (NTD) in 54% of cases, comprising isolated tail flexion defects and spina bifida with tail flexion defects. Both types of spinal NTD result from delayed closure of the posterior neuropore (PNP). Previous studies (Seller et al. El9791 Proc. R. SOC. Lond. Biol. 20695-107; Seller and Perkins [19821 Prenat. Diagn. 2297300) described a paradoxial effect of retinoic acid (RA) on the phenotypic expression of the ct mutation: Treatment with low doses of RA on day 8 of gestation increased the incidence of total NTD, whereas low doses of RA administered on day 9 resulted in reduced incidence of total NTD. In order to investigate further the reported preventive effect of RA, we have carried out detailed analyses of the effects of maternal treatment with 5 mg/kg RA on the incidence of NTD at different developmental stages, and on the development and growth of ctlct embryos. We found that 5 mg/kg RA reduces the incidence of spinal NTD in a stage-specific manner, without increasing the incidence of cranial NTD. The effect of RA is specific: There were no other alterations in morphogenesis, growth, development, resorption rate, or litter size. RA was more effective in the prevention of isolated tail flexion defects than of spina bifida. Prevention of isolated tail flexion defects was maximal (50% reduction) when RA was administered between 10 days 4 hours and 10 days 8 hours post coitum (P.c.) inclusive (24 to 34 somite stage). In contrast, maximal prevention of spina bifida (36%) resulted from RA administration at 10 days 8 hours P.c.; decreased PNP size in treated embryos, compared with control embryos, was evident by 6 hours after the treatment at the 27 to 31 somite stage. The preventive effect of RA on spina bifida was related to maternal phenotype: By comparison with phenotypically straighttailed mothers, curly-tailed mothers had a greater incidence of spina bifida among their offspring, and this incidence was unresponsive to RA. This result suggests that additional factors, such as modifier genes, modulating phenotypic expression of the ct gene, may be present in the ct mutant stock. Here we show that the RA prevention of spinal NTD is a specific effect. Hence it is plausi-0 1994 WILEY-LISS, INC. ble that this prevention of spinal NTD by RA is mediated via nuclear retinoic acid receptors.

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Section: Penetrance Of Spina Bifida and Its Prevention By Ra Depend Osupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Prevention of spinal neural tube defects in the curly tail mouse mutant by a specific effect of retinoic acid

Chen

Morriss‐Kay

Copp

1994

Developmental Dynamics

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“…2D,DЈ), 89% of embryos extracted at E11.5 or later presented with a curly tail phenotype (Fig. 2F), indicative of a defect in secondary neurulation in the rostral region of the neural tube (Embury et al, 1979), and one Spint2 -/-embryo suffered from an incomplete closure of the neural tube in the back region (spina bifida; Fig. 2F).…”

Section: Spint2 Promotes Placental Branching Morphogenesis and Neuralmentioning

confidence: 99%

Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice

et al. 2009

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Hypomorphic mutations in the human SPINT2 gene cause a broad spectrum of abnormalities in organogenesis, including organ and digit duplications, atresia, fistulas, hypertelorism, cleft palate and hamartoma. SPINT2 encodes the transmembrane serine protease inhibitor HAI2 (placental bikunin), and the severe developmental effects of decreased HAI2 activity can be hypothesized to be a consequence of excess pericellular proteolytic activity. Indeed, we show here that HAI2 is a potent regulator of protease-guided cellular responses, including motogenic activity and transepithelial resistance of epithelial monolayers. Furthermore, we show that inhibition of the transmembrane serine protease matriptase (encoded by St14) is an essential function of HAI2 during tissue morphogenesis. Genetic inactivation of the mouse Spint2 gene led to defects in neural tube closure, abnormal placental labyrinth development associated with loss of epithelial cell polarity, and embryonic demise. Developmental defects observed in HAI2-deficient mice were caused by unregulated matriptase activity, as both placental development and embryonic survival in HAI2-deficient embryos were completely restored by the simultaneous genetic inactivation of matriptase. However, neural tube defects were detected in HAI2-deficient mice even in the absence of matriptase, although at lower frequency, indicating that the inhibition of additional serine protease(s) by HAI2 is required to complete neural development. Finally, by genetic complementation analysis, we uncovered a unique and complex functional interaction between HAI2 and the related HAI1 in the regulation of matriptase activity during development. This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development.

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“…One of these mouse mutants, curly tail (ct) (6), has been extensively studied as the best available model for human NTD. NTD in ct mice closely resemble the human malformation in many respects, including their location and form (6,7) and mode of multifactorial inheritance (6,8).…”

Section: Introductionmentioning

confidence: 99%

Neural tube defects and abnormal brain development in F52-deficient mice.

Chen

Sasaoka

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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F52 is a myristoylated, alanine-rich substrate for protein kinase C. We have generated F52-deficient mice by the gene targeting technique. These mutant mice manifest severe neural tube defects that are not associated with other complex malformations, a phenotype reminiscent of common human neural tube defects. The neural tube defects observed include both exencephaly and spina bifida, and the phenotype exhibits partial penetrance with about 60% of homozygous embryos developing neural tube defects. Exencephaly is the prominent type of defect and leads to high prenatal lethality. Neural tube defects are observed in a smaller percentage of heterozygous embryos (about 10%). Abnormal brain development and tail formation occur in homozygous mutants and are likely to be secondary to the neural tube defects. Disruption of F52 in mice therefore identifies a gene whose mutation results in isolated neural tube defects and may provide an animal model for common human neural tube defects.

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Neural tube defects in curly-tail mice. I. Incidence, expression and similarity to the human condition

Cited by 59 publications

References 10 publications

Prevention of spinal neural tube defects in the curly tail mouse mutant by a specific effect of retinoic acid

Prevention of spinal neural tube defects in the curly tail mouse mutant by a specific effect of retinoic acid

Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice

Neural tube defects and abnormal brain development in F52-deficient mice.

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