Novel exomphalos genetic mouse model: the importance of accurate phenotypic classification

Helen Carnaghan; Tom Roberts; Dawn Savery; Francesca C Norris; Conor J McCann; Andrew J Copp; Peter J Scambler; Mark F Lythgoe; Nicholas D Greene; Paolo Decoppi; Alan J Burns; Agustino Pierro; Simon Eaton

doi:10.1016/j.jpedsurg.2013.04.010

Novel exomphalos genetic mouse model: the importance of accurate phenotypic classification

Helen Carnaghan, Tom Roberts, Dawn Savery, Francesca C Norris, Conor J McCann, Andrew J Copp, Peter J Scambler, Mark F Lythgoe, Nicholas D Greene, Paolo Decoppi, Alan J Burns, Agustino Pierro, Simon Eaton

Perinatal Imaging & Health

UCL Institute of Child Health, London, UK; Department of Histopathology, UCL Institute of Child Health & Great Ormond Street Hospital for Children, London, UK.

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

BACKGROUND: Rodent models of abdominal wall defects (AWD) may provide insight into the pathophysiology of these conditions including gut dysfunction in gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis. We further characterise this AWD in Scribble knockout mice.

METHOD: Homozygous Scrib knockout mice were obtained from heterozygote matings. Fetuses were collected at E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed and gut length/weight measured. Ileal specimens were stained for interstitial cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified.

RESULTS: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered gut/liver herniation into the umbilical cord. A further 12 exhibited extensive AWD, with eviscerated abdominal organs and thin covering membrane (intact or ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in AWD group compared to controls but morphology/number of ICC was not different.

DISCUSSION: The Scribble knockout fetus exhibits exomphalos (intact and ruptured), in contrast to the original published phenotype of gastroschisis. Detailed dissection of fetuses is essential ensuring accurate phenotyping and result reporting.

Original language	English
Pages (from-to)	2036-42
Number of pages	7
Journal	Journal of Pediatric Surgery
Volume	48
Issue number	10
DOIs	https://doi.org/10.1016/j.jpedsurg.2013.04.010
Publication status	Published - Oct 2013

Keywords

Abdominal Wall/abnormalities
Animals
Disease Models, Animal
Dissection/methods
Gastroschisis/classification
Genetic Markers
Hernia, Umbilical/classification
Interstitial Cells of Cajal/pathology
Intracellular Signaling Peptides and Proteins/deficiency
Magnetic Resonance Imaging/methods
Mice
Mice, Knockout
Phenotype

Access to Document

10.1016/j.jpedsurg.2013.04.010

Cite this

Carnaghan, H., Roberts, T., Savery, D., Norris, F. C., McCann, C. J., Copp, A. J., Scambler, P. J., Lythgoe, M. F., Greene, N. D., Decoppi, P., Burns, A. J., Pierro, A., & Eaton, S. (2013). Novel exomphalos genetic mouse model: the importance of accurate phenotypic classification. Journal of Pediatric Surgery, 48(10), 2036-42. https://doi.org/10.1016/j.jpedsurg.2013.04.010

@article{a8c74e0a2eec4a44af03ffb8829b690d,

title = "Novel exomphalos genetic mouse model: the importance of accurate phenotypic classification",

abstract = "BACKGROUND: Rodent models of abdominal wall defects (AWD) may provide insight into the pathophysiology of these conditions including gut dysfunction in gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis. We further characterise this AWD in Scribble knockout mice.METHOD: Homozygous Scrib knockout mice were obtained from heterozygote matings. Fetuses were collected at E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed and gut length/weight measured. Ileal specimens were stained for interstitial cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified.RESULTS: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered gut/liver herniation into the umbilical cord. A further 12 exhibited extensive AWD, with eviscerated abdominal organs and thin covering membrane (intact or ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in AWD group compared to controls but morphology/number of ICC was not different.DISCUSSION: The Scribble knockout fetus exhibits exomphalos (intact and ruptured), in contrast to the original published phenotype of gastroschisis. Detailed dissection of fetuses is essential ensuring accurate phenotyping and result reporting.",

keywords = "Abdominal Wall/abnormalities, Animals, Disease Models, Animal, Dissection/methods, Gastroschisis/classification, Genetic Markers, Hernia, Umbilical/classification, Interstitial Cells of Cajal/pathology, Intracellular Signaling Peptides and Proteins/deficiency, Magnetic Resonance Imaging/methods, Mice, Mice, Knockout, Phenotype",

author = "Helen Carnaghan and Tom Roberts and Dawn Savery and Norris, {Francesca C} and McCann, {Conor J} and Copp, {Andrew J} and Scambler, {Peter J} and Lythgoe, {Mark F} and Greene, {Nicholas D} and Paolo Decoppi and Burns, {Alan J} and Agustino Pierro and Simon Eaton",

year = "2013",

month = oct,

doi = "10.1016/j.jpedsurg.2013.04.010",

language = "English",

volume = "48",

pages = "2036--42",

journal = "Journal of Pediatric Surgery",

issn = "0022-3468",

publisher = "W.B. Saunders Ltd",

number = "10",

}

TY - JOUR

T1 - Novel exomphalos genetic mouse model

T2 - the importance of accurate phenotypic classification

AU - Carnaghan, Helen

AU - Roberts, Tom

AU - Savery, Dawn

AU - Norris, Francesca C

AU - McCann, Conor J

AU - Copp, Andrew J

AU - Scambler, Peter J

AU - Lythgoe, Mark F

AU - Greene, Nicholas D

AU - Decoppi, Paolo

AU - Burns, Alan J

AU - Pierro, Agustino

AU - Eaton, Simon

PY - 2013/10

Y1 - 2013/10

N2 - BACKGROUND: Rodent models of abdominal wall defects (AWD) may provide insight into the pathophysiology of these conditions including gut dysfunction in gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis. We further characterise this AWD in Scribble knockout mice.METHOD: Homozygous Scrib knockout mice were obtained from heterozygote matings. Fetuses were collected at E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed and gut length/weight measured. Ileal specimens were stained for interstitial cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified.RESULTS: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered gut/liver herniation into the umbilical cord. A further 12 exhibited extensive AWD, with eviscerated abdominal organs and thin covering membrane (intact or ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in AWD group compared to controls but morphology/number of ICC was not different.DISCUSSION: The Scribble knockout fetus exhibits exomphalos (intact and ruptured), in contrast to the original published phenotype of gastroschisis. Detailed dissection of fetuses is essential ensuring accurate phenotyping and result reporting.

AB - BACKGROUND: Rodent models of abdominal wall defects (AWD) may provide insight into the pathophysiology of these conditions including gut dysfunction in gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis. We further characterise this AWD in Scribble knockout mice.METHOD: Homozygous Scrib knockout mice were obtained from heterozygote matings. Fetuses were collected at E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed and gut length/weight measured. Ileal specimens were stained for interstitial cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified.RESULTS: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered gut/liver herniation into the umbilical cord. A further 12 exhibited extensive AWD, with eviscerated abdominal organs and thin covering membrane (intact or ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in AWD group compared to controls but morphology/number of ICC was not different.DISCUSSION: The Scribble knockout fetus exhibits exomphalos (intact and ruptured), in contrast to the original published phenotype of gastroschisis. Detailed dissection of fetuses is essential ensuring accurate phenotyping and result reporting.

KW - Abdominal Wall/abnormalities

KW - Animals

KW - Disease Models, Animal

KW - Dissection/methods

KW - Gastroschisis/classification

KW - Genetic Markers

KW - Hernia, Umbilical/classification

KW - Interstitial Cells of Cajal/pathology

KW - Intracellular Signaling Peptides and Proteins/deficiency

KW - Magnetic Resonance Imaging/methods

KW - Mice

KW - Mice, Knockout

KW - Phenotype

U2 - 10.1016/j.jpedsurg.2013.04.010

DO - 10.1016/j.jpedsurg.2013.04.010

M3 - Article

C2 - 24094954

SN - 0022-3468

VL - 48

SP - 2036

EP - 2042

JO - Journal of Pediatric Surgery

JF - Journal of Pediatric Surgery

IS - 10

ER -

Novel exomphalos genetic mouse model: the importance of accurate phenotypic classification

Abstract

Keywords

Access to Document

Fingerprint

Cite this