Reference SummaryJhappan C, Genes Dev 1992 Mar;6(3):345-55

Title

 Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.

Authors

 Jhappan C; Gallahan D; Stahle C; Chu E; Smith GH; Merlino G; Callahan R

Journal

 Genes Dev

Volume

 6

Issue

 3

Year

 1992

Pages

 345-55

Abstract

 Expression of the int-3 locus is activated in mouse mammary tumors as a consequence of insertional mutagenesis by the mouse mammary tumor virus (MMTV). Integration of the MMTV provirus into the int-3 locus promotes the transcription and translation of flanking cellular int-3 sequences sharing significant homology with the intracellular domain of the neurogenic Notch gene of Drosophila, and with the yeast cell cycle regulatory genes cdc10 and SWI6. To determine the in vivo consequences of activated int-3 expression, transgenic mice were generated harboring a genomic tumor DNA fragment consisting of the MMTV LTR and the flanking cellular int-3 sequences. All six int-3 founder transgenic mice and the progeny of one established line exhibited similar dramatic phenotypic abnormalities in tissues in which the transgene was expressed. Focal and often multiple poorly differentiated mammary and salivary adenocarcinomas appeared in the majority of transgenic mice between 2 and 7 months of age. Significantly, mammary glands were arrested in development and were lactation deficient in all female int-3 mice. The salivary glands, glands of the nasal mucosa and maxillary sinus, the extraorbital lacrimal glands, and the Harderian glands of juvenile and adult transgenic mice all contained proliferating immature ductule cells and were incompletely differentiated. In addition, all male int-3 transgenic mice were sterile, apparently the result of severe hyperplasia of the epididymis. These findings demonstrate in vivo that expression of the activated Notch-related int-3 gene causes deregulation of normal developmental controls and hyperproliferation of glandular epithelia.

Links

 J:11644 – MGI References
1372276 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N-Tg(MMTV-Notch4)3Rnc Expression of the "MMTVInt3" transgene was reported to not be detected in the liver, kidneys, skeletal muscle, spleen, lungs, heart, brain, stomach, pancreas, or ovaries of these mice.
Expression of the "MMTVInt3" transgene was reported to not be detected n the preputial gland, seminal vesicle, testis, thymus, salivary glands, and mammary glands of these mice.
Female mice show an inability to lactate.
Male mice are sterile.
The "MMTVInt3" transgene was reported to be highly expressed n the Harderian glands of these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(MMTV-Notch4)3Rnc Epididymis hyperplasia Epididymis

100
FVB/N-Tg(MMTV-Notch4)3Rnc Eye - Harderian gland hyperplasia Eye - Harderian gland

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Eye - Lacrimal gland hyperplasia Eye - Lacrimal gland

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Leukocyte - Lymphoblast lymphoma - lymphoblastic Thymus

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Mammary gland adenocarcinoma Mammary gland

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Mammary gland hyperplasia Mammary gland

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Nose - Nasal cavity - Nasal gland hyperplasia Nose - Nasal cavity - Nasal gland

observed
FVB/N Nose - Nasal cavity - Nasal gland hyperplasia Nose - Nasal cavity - Nasal gland

0
FVB/N-Tg(MMTV-Notch4)3Rnc Prostate gland - Anterior lobe hyperplasia Prostate gland - Anterior lobe

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Salivary gland adenocarcinoma Salivary gland

observed
FVB/N-Tg(MMTV-Notch4)3Rnc Salivary gland hyperplasia Salivary gland

very high