Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse

Dietrich, William F.; Lander, Eric S.; Smith, Jennifer S.; Moser, Amy R.; Gould, Karen A.; Luongo, Cindy; Borenstein, Natalie; Dove, William F.

doi:10.1016/0092-8674(93)90484-8

Cited by 605 publications

(367 citation statements)

References 39 publications

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“…In addition, a subset was assayed as described 25 for Mom1, a known modifier of tumor number. 24 All progeny tested (10/10) were homozygous (data not shown) for the susceptible allele present in the C57BL/6 strain.…”

Section: Micementioning

confidence: 93%

“…The median number of adenomas present in the intestinal tract of Apc Min/1 ; Gucy2c 2/2 mice (n 5 12) was 16 (range, 7-26). This is a decrease of 55% compared to the median of 29 polyps (range, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] observed in Apc Min/1 ; Gucy2c 1/1 mice (n 5 7; p < 0.006). A third of the Apc Min/1 ; Gucy2c 2/2 mice (4/12) exhibited polyp numbers within the range of the Apc Min/1 ; Gucy2c 1/1 group and so may reflect the action of modifier genes contributed by non-C57BL/6 loci still segregating in these mice (see Material and Methods).…”

Section: Fewer Polyps In Gc-c-deficient Min Micementioning

confidence: 99%

“…One strategy has employed naturally occurring mouse strain DNA polymorphisms to identify loci that affect the latency or multiplicity of tumors. This has resulted in the identification of the Mom1 region on chromosome 4 24 and the Mom2 locus on chromosome 18. 25 Another approach to investigating modifiers of Apc Min has been to test the effect of the lack of a candidate gene on tumor number.…”

mentioning

confidence: 99%

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Lack of guanylyl cyclase C, the receptor for Escherichia coli heat‐stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model

Mann

Steinbrecher

Stroup

et al. 2005

Intl Journal of Cancer

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Guanylyl cyclase C (GC-C), a transmembrane receptor for bacterial heat-stable enterotoxin and the mammalian peptides guanylin and uroguanylin, mediates intestinal ion secretion and affects intestinal cell growth via cyclic GMP signaling. In intestinal tumors, GC-C expression is maintained while guanylin and uroguanylin expression is lost, suggesting a role for GC-C activation in tumor formation or growth. We show by in situ hybridization that GC-C expression is retained in adenomas from multiple intestinal neoplasia (Apc Min/+ ) mice. In order to determine the in vivo role of GC-C in intestinal tumorigenesis, we generated Apc Min/+ mice homozygous for a targeted deletion of the gene encoding GC-C and hypothesized that these mice would have increased tumor multiplicity and size compared to wild-type Apc Min/+ mice on the same genetic background. In contrast, the absence of GC-C resulted in a reduction of median polyp number by 55%. There was no change in the median diameter of polyps, suggesting no effect on tumor growth. Somatic loss of the wild-type Apc allele, an initiating event in intestinal tumorigenesis, also occurred in polyps from GC-C-deficient Apc Min/+ mice. We have found increased levels of apoptosis as well as increased caspase-3 and caspase-7 gene expression in the intestines of GC-C-deficient Apc Min/+ mice compared with Apc Min/+ mice. We propose that these alterations are a possible compensatory mechanism by which loss of GC-C signaling also affects tumorigenesis. Published 2005 Wiley-Liss, Inc.

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Section: Micementioning

confidence: 93%

Section: Fewer Polyps In Gc-c-deficient Min Micementioning

confidence: 99%

mentioning

confidence: 99%

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Lack of guanylyl cyclase C, the receptor for Escherichia coli heat‐stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model

Mann

Steinbrecher

Stroup

et al. 2005

Intl Journal of Cancer

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“…The most established one is the modi®er of Min locus (Mom1) (Dietrich et al, 1993). Combination of Min and Mom1 leads to an increase of lifespan and reduced tumor number.…”

Section: Genetic Basis For Colorectal Cancermentioning

confidence: 99%

Mouse models for colorectal cancer

et al. 1999

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“…As has been achieved in simpler organisms such as D. melanogaster, the undertaking of genetic modi®er screens in the mouse is now possible. The ®rst modi®er to have been identi®ed and cloned is the phospholipase A2 (PLAP2) locus which a ects polyp number in the APC Min model (Dietrich et al, 1993;MacPhee et al, 1995). Large scale screens to identify and ultimately clone modi®ers of a number of phenotypes is now underway in the mouse, including the search for genes that modify metastasis phenotype.…”

Section: The Futurementioning

confidence: 99%

Modeling metastasis in the mouse

McClatchey

1999

Oncogene

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Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse

Cited by 605 publications

References 39 publications

Lack of guanylyl cyclase C, the receptor for Escherichia coli heat‐stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model

Lack of guanylyl cyclase C, the receptor for Escherichia coli heat‐stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model

Mouse models for colorectal cancer

Modeling metastasis in the mouse

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