The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the role Notch4 gene, we generated Notch4-deficient mice by targeting. Embryos homozygous for this mutation developed normally, and mutant adults were viable fertile. However, displayed genetic interactions with a targeted related Notch1 gene. mutations both genes often more severe phenotype than embryos. Both Notch1/Notch4 double embryos...

Any epithelial portion of a normal mouse mammary gland can reproduce an entire functional when transplanted into epithelium-free fat pad. Mouse hyperplasias and tumors are clonal dominant populations probably represent the progeny single transformed cell. Our study provides evidence that multipotent stem cells positioned throughout mature fully developed have capacity to produce sufficient differentiated recapitulate gland. also demonstrates these self-renewing found with undiminished...

Expression of the int-3 locus is activated in mouse mammary tumors as a consequence insertional mutagenesis by tumor virus (MMTV). Integration MMTV provirus into promotes transcription and translation flanking cellular sequences sharing significant homology with intracellular domain neurogenic Notch gene Drosophila, yeast cell cycle regulatory genes cdc10 SWI6. To determine vivo consequences expression, transgenic mice were generated harboring genomic DNA fragment consisting LTR sequences....

It has been postulated that the stem cells of somatic tissues protect themselves from mutation and cancer risk by selective segregation their template DNA strands. Self-renewing mammary epithelial were originated during allometric growth ducts in pubertal females labeled using [3H]-thymidine (3HTdR). After a prolonged chase which much branching duct morphogenesis was completed, 3HTdR-label retaining (LREC) detected among epithelium maturing glands. Labeling newly synthesized these glands...

Postnatal development of the mammary gland begins during puberty with ductal proliferation and is completed at delivery appearance secretory alveolar structures. Using endogenous milk protein genes a WAP-lacZ reporter transgene, we show that differentiation cells initiated in virgin mice estrus limited number cells. With onset pregnancy, expressing cellular expression levels increase until full activity reached lactation. Milk are activated defined temporal sequence. WDNM1 beta-casein...

Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined specific contributions receptor (PrlR) signal transducers activators transcription 5a 5b (referred to as Stat5) in formation differentiation alveolar epithelium. PrlR- Stat5-null epithelia were transplanted into wild-type hosts, pregnancy-mediated was investigated at a histological level. developed ducts but...

Mammary gland biologists have long assumed that differentiated secretory epithelial cells undergo programmed cell death at the end of lactation and alveolar compartment is reconstituted from undifferentiated precursor in subsequent pregnancies. It generally agreed remodeled a parous animal resembles mature virgin morphological level. However, several physiological differences been noted comparing responses mammary epithelia nulliparous versus females to hormonal stimulation carcinogenic...

Transplantation studies demonstrate that an epithelial stem cell component must exist in the mouse mammary gland throughout life. Samples taken from any portion of at age and developmental stage, including full functional differentiation, give rise to outgrowths with complete capacity. Cytological examination explants revealed presence morphologically distinct cells distributed sporadically among epithelium, whose behaviour vivo vitro suggested they might represent a latent population. These...

Previously, we characterized a parity-induced mammary epithelial cell population that possessed the properties of pluripotency and self-renewal upon transplantation. These cells were lineally marked by expression beta-galactosidase (LacZ) as result mammary-specific activation reporter gene through Cre-lox recombination during pregnancy. We used this experimental model to determine whether testicular would alter their fate interaction with gland microenvironment pregnancy, lactation,...

Over nearly half a century, transplantation methods have been employed to regenerate the mammary gland in vivo. Recent highly cited reports claim demonstrated regeneration of an entire functional from single epithelial cell. Nevertheless, re-examination literature on biology reveals that complex, combinatorial interaction between variously differentiated cells and fat pad stroma is indispensable this process. In present article, these issues are reviewed discussed provide greater...

Abstract Examination of various normal and neoplastic tissues reveals the presence intracisternal A‐particles in five strains mice their hybrids. Cell types derived from all three embryonic germ layers contain these particles, gonadal tissue both sexes suggests that vertical transmission can take place. Intracisternal are found most known to support replication mouse leukemia viruses mammary tumor virus. Further, they have been shown coexist same cell with C particles intracytoplasmic...

With a unique mouse mammary tumor model system in which virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered new common integration site (designated Int-6) for MMTV tumors. was integrated into Int-6 hyperplastic outgrowth line, its tumors and metastases, two independent arising unrelated mice. The gene is ubiquitously expressed as 1.4-kb RNA species adult tissues beginning at day 8 of embryonic...

A fundamental issue in stem cell biology is whether adult somatic cells are capable of accessing alternate tissue sites and continue functioning as the new microenvironment. To address this relative to neurogenic mouse mammary gland microenvironment, we mixed wild-type epithelial (MECs) with bona fide neural (NSCs) isolated from WAP-Cre/Rosa26R mice inoculated them into cleared fat pads immunocompromised females. Hosts were bred 6-8 weeks later examined postinvolution. This allowed for...

Abstract Introduction Stem cells of somatic tissues are hypothesized to protect themselves from mutation and cancer risk through a process selective segregation their template DNA strands during asymmetric division. Mouse mammary epithelium contains label-retaining epithelial that divide asymmetrically retain DNA. Method Immunohistochemistry was used in murine glands had been labeled with [ 3 H]thymidine allometric growth investigate the co-expression label retention estrogen receptor (ER)-α...