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A staging system for correct phenotype interpretation of mouse embryos harvested on embryonic day 14 (E14.5)

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ABSTRACT

We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely on the external appearance of the maturing forelimb, we provide a convenient way to distinguish six developmental sub‐stages. Using a variety of objective morphometric data obtained from the commonly used C57BL/6N mouse strain, we show that these stages correlate precisely with the growth of the entire embryo and its organs. Applying the new staging system to phenotype analyses of E14.5 embryos of 58 embryonic lethal mutant lines from the DMDD research programme (https://dmdd.org.uk) and its pilot, we show that homozygous mutant embryos are frequently delayed in development. To demonstrate the importance of our staging system for correct phenotype interpretation, we describe stage‐specific changes of the palate, heart and gut, and provide examples in which correct diagnosis of malformations relies on correct staging.

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Impact of stage variations on phenotype scores. (A,B) Cleft palate in a control embryo (S22) and Chst11 mutant (S23−) (C,D) embryo (S23) and a 17000667K01Rik mutant (S22+) (C,D). The inlays show corresponding handplates. (E,F) Volume‐rendering (E) and original axial HREM‐section showing abnormal placement of the intestine in an Ssr2 mutant. co, colon; j, jejunum.
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joa12590-fig-0005: Impact of stage variations on phenotype scores. (A,B) Cleft palate in a control embryo (S22) and Chst11 mutant (S23−) (C,D) embryo (S23) and a 17000667K01Rik mutant (S22+) (C,D). The inlays show corresponding handplates. (E,F) Volume‐rendering (E) and original axial HREM‐section showing abnormal placement of the intestine in an Ssr2 mutant. co, colon; j, jejunum.

Mentions: An example, of such diagnosis is the Chst11 knock‐out line, shown in Figure 5. Both the control (S22) and mutant (S23−) embryos appear to show cleft palate, but because of differences in their precise developmental stage, only the mutant can be scored with confidence as having palatine cleft (Fig. 5A,B).


A staging system for correct phenotype interpretation of mouse embryos harvested on embryonic day 14 (E14.5)
Impact of stage variations on phenotype scores. (A,B) Cleft palate in a control embryo (S22) and Chst11 mutant (S23−) (C,D) embryo (S23) and a 17000667K01Rik mutant (S22+) (C,D). The inlays show corresponding handplates. (E,F) Volume‐rendering (E) and original axial HREM‐section showing abnormal placement of the intestine in an Ssr2 mutant. co, colon; j, jejunum.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382591&req=5

joa12590-fig-0005: Impact of stage variations on phenotype scores. (A,B) Cleft palate in a control embryo (S22) and Chst11 mutant (S23−) (C,D) embryo (S23) and a 17000667K01Rik mutant (S22+) (C,D). The inlays show corresponding handplates. (E,F) Volume‐rendering (E) and original axial HREM‐section showing abnormal placement of the intestine in an Ssr2 mutant. co, colon; j, jejunum.
Mentions: An example, of such diagnosis is the Chst11 knock‐out line, shown in Figure 5. Both the control (S22) and mutant (S23−) embryos appear to show cleft palate, but because of differences in their precise developmental stage, only the mutant can be scored with confidence as having palatine cleft (Fig. 5A,B).

View Article: PubMed Central - PubMed

ABSTRACT

We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely on the external appearance of the maturing forelimb, we provide a convenient way to distinguish six developmental sub‐stages. Using a variety of objective morphometric data obtained from the commonly used C57BL/6N mouse strain, we show that these stages correlate precisely with the growth of the entire embryo and its organs. Applying the new staging system to phenotype analyses of E14.5 embryos of 58 embryonic lethal mutant lines from the DMDD research programme (https://dmdd.org.uk) and its pilot, we show that homozygous mutant embryos are frequently delayed in development. To demonstrate the importance of our staging system for correct phenotype interpretation, we describe stage‐specific changes of the palate, heart and gut, and provide examples in which correct diagnosis of malformations relies on correct staging.

No MeSH data available.


Related in: MedlinePlus