Association of Megacolon with Two Recessive Spotting Genes in the Mouse

Lane, Priscilla W.

doi:10.1093/oxfordjournals.jhered.a107457

Cited by 182 publications

(85 citation statements)

References 7 publications

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“…Whereas mice homozygous for a null mutation of EDNRB always exhibit intestinal aganglionosis, s/s mice rarely show intestinal aganglionosis. Interestingly, compound heterozygous mice (s/Ϫ) exhibit distal intestinal aganglionosis in ‫ف‬ 19% of pups (our unpublished observations) (10). The compound heterozygous mice have been shown by Northern analysis to express 12.5% the level of EDNRB mRNA as wild-type mice.…”

Section: Discussionmentioning

confidence: 76%

“…Incomplete melanoblast colonization of the skin results in pigmentary abnormalities. The colonization processes of melanoblasts and ENS precursors are influenced by overlapping genetic pathways as evidenced by hereditary syndromes in which defects in development of both lineages appear together as localized pigment abnormalities associated with intestinal aganglionosis (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.

Gariepy¹,

Williams²,

Richardson³

et al. 1998

J. Clin. Invest.

164

145

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The spotting lethal rat, a naturally occurring rodent model of Hirschsprung disease, carries a deletion in the endothelin-B receptor ( EDNRB ) gene that abrogates expression of functional EDNRB receptors. Rats homozygous for this mutation ( sl ) exhibit coat color spotting and congenital intestinal aganglionosis. These deficits result from failure of the neural crest-derived epidermal melanoblasts and enteric nervous system (ENS) precursors to completely colonize the skin and intestine, respectively. We demonstrate that during normal rat development, the EDNRB mRNA expression pattern is consistent with expression by ENS precursors throughout gut colonization. We used the human dopamine-␤ -hydroxylase ( D ␤ H ) promoter to direct transgenic expression of EDNRB to colonizing ENS precursors in the sl/sl rat. The D ␤ H-EDNRB transgene compensates for deficient endogenous EDNRB in these rats and prevents the intestinal defect. The transgene has no effect on coat color spotting, indicating the critical time for EDNRB expression in enteric nervous system development begins after separation of the melanocyte lineage from the ENS lineage and their common precursor. The transgene dosage affects both the incidence and severity of the congenital intestinal defect, suggesting dosage-dependent events downstream of EDNRB activation in ENS development.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.

Gariepy¹,

Williams²,

Richardson³

et al. 1998

J. Clin. Invest.

164

145

View full text Add to dashboard Cite

show abstract

“…There are multiple mouse genes, which, when mutated, result in aganglionosis restricted to the colon (Lane, 1966;Webster, 1973;Baynash et al, 1994;Herbarth et al, 1998;Hosoda et al, 1994;Yanagisawa et al, 1998;de Graaff et al, 2001;Breau et al, 2006). Two mouse models that have been used extensively and closely resemble the human phenotype are piebald-lethal mice that lack Ednrb expression (Ednrb sl/sl ) and lethal-spotted mice that lack Edn3 expression (Edn3 ls/ls ) Baynash et al, 1994;Gariepy et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors

2009

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“…Another recessive spotting gene, the lethal spotting (Is) gene, is not allelic with s but resembles its effect on coat pigmentation. A few Is/Is mice have lived to reproduce; however, all eventually die with megacolon as a result of aganglionosis of the distal colon [8,II).…”

Section: Discussionmentioning

confidence: 99%

Congenital Intestinal Aganglionosis in White Foals

1983

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Abstract. A congenital and probably hereditary neurological defect has been identified in the intestinal tract of six foals produced from the breeding of overo (a type of spotting pattern) horses. The foals had white hair and pink skin with the exception of occasional pigmented foci about the muzzle, ventral abdomen, and hindquarters. The foals appeared normal at birth, but within a few hours developed symptoms of colic. At necropsy, the only significant finding was a narrow, pale segment of large intestine. This abnormality either was confined to the small colon and rectum or involved the entire colon and rectum. Microscopically, myenteric and submucosal neuronal plexuses were absent throughout the large intestine and extensive portions of the small intestine. The only other significant finding was the lack of melanin in the skin.Two recognized spotting patterns, tobiano ( fig. 1) and overo (fig. 2) are eligible for registration in stud books of the American Paint Horse Association and the Pinto Horse Association of America. These patterns also occur in several other breeds of horses (16]. The mating of two overo horses occasionally results in the production of a white foal which appears normal at birth; however, the foal fails to pass meconium, quickly develops colic, and dies. Stenosis of the colon [7], rectal atresia (15], and a paucity of ganglia in the transverse colon [15] have been reported in these foals. A recent report describes aganglionosis of colon and terminal ileum in white foals from overo parents [6]. This paper describes the clinical and pathologic findings in six white foals. Case HistoriesClinical histories of the foals in this study are summarized in table I. All foals were produced by overo X overo matings with the exception of foal I. Initial records indicated this foal had an overo dam and was sired by a tobiano stallion which had been sired by an overo stallion. Unfortunately, the owner could not be contacted to confirm this. Foals 2 and 6 had the same dam; however, each was sired by a different stallion.The foals had white hair and pink skin with the exception of occasional black tail 65

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Association of Megacolon with Two Recessive Spotting Genes in the Mouse

Cited by 182 publications

References 7 publications

Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.

Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.

Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors

Congenital Intestinal Aganglionosis in White Foals

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