Phenotypic Resemblance Research Articles

Female-limited polymorphism in a widespread damselfly: morph frequencies, male density, and phenotypic similarity of andromorphs to males

In several animal species, one male type coexists with two to several female types, a polymorphism often explained in the context of sexual selection. Where it occurs, one female morph typically resembles the conspecific male phenotype, but the degree of resemblance varies across species. Here, we question whether the degree of phenotypic similarity between male-like females and males varies within species. Phenotypic resemblance is hypothesized to depend on the potential for frequency- and density-dependent selection on male and (or) female phenotypes. We studied six populations of the damselfly Nehalennia irene (Hagen, 1861) that differed widely in estimates of morph frequency and male density. Male-like females resemble males more than another female type resembles males, across populations, when comparisons are based on abdominal patterns. Abdomen phenotype does matter in male–female interactions of damselflies. Furthermore, male-like females were more similar to males at low and high density sites compared with sites with intermediate densities, contrary to the hypothesis that the potential for male harassment influences the degree of phenotypic similarity. Additionally, male-like females of most populations converged on the abdominal phenotype of males of one population rather than on that of syntopic males; a problem that has not received any attention.

Non-cultured adipose-derived CD45− side population cells are enriched for progenitors that give rise to myofibres in vivo

Side population (SP) cells are highly able to exclude the Hoechst 33342 dye through membrane transporters, a feature associated with cell immaturity and therefore proposed as a marker of stem cells. Herein we demonstrate that the adipose tissue derived stromal vascular fraction (SVF) contains a novel population of non-haematopoietic “side population” (SPCD45−) cells. Simultaneous qRT-PCR of 64 genes revealed that the freshly isolated SPCD45− was highly enriched for cells expressing genes related to stem cells, the Notch pathway, and early vascular precursors. Notably, the expression of smooth muscle actin, C-met and Cd34 together with Angpt2, Flk1, VE-cadherin, and Cd31 suggested a phenotypic resemblance to pericytes and aorta-derived mesoangioblasts. Recent evidence suggests that cells residing within the vascular niche may participate in regeneration of skeletal muscle and although skeletal muscle repair mainly relies on the satellitecell, several reports have shown that vessel-associated cells may adopt a myogenic phenotype when exposed to a muscle environment. In accordance with these findings, we also observed invitro myogenic specification of SPCD45− cells when cocultured with myoblasts. Furthermore, immediate intramuscular engraftment of non-cultured SPCD45− cells gave rise to myofibres andcells lining blood vessels, whereas the SVF only provided donor derived mononuclear cells. We therefore conclude that the SPCD45− fraction of adipose-derived SVF is enriched for cells expressing vascular associated markers and that the myogenic differentiation potential of these cells does not depend on prior in vitro expansion.

Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival

Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-beta staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

Barren inflorescence1 Functions in Organogenesis During Vegetative and Inflorescence Development in Maize

Maize (Zea mays) has a highly branched inflorescence due to the production of different types of axillary meristems. Characterization of the barren inflorescence class of mutants has led to the discovery of genes required for axillary meristem initiation in the inflorescence. Previous studies showed that barren inflorescence2 (bif2) encodes a serine/threonine protein kinase that regulates auxin transport, and barren stalk1 (ba1) encodes a basic helix-loop-helix transcription factor that acts downstream of auxin transport. Here, we characterize Barren inflorescence1 (Bif1), a classical semidominant mutation of maize. Developmental, histological, and genetic analyses show that Bif1 mutants are defective in the initiation of all axillary meristems in the inflorescence. Real time RT-PCR experiments show that both bif2 and ba1 are expressed at lower levels in Bif1 mutants. Double-mutant analyses demonstrate that Bif1 exhibits an epistatic interaction with ba1 and a synergistic interaction with bif2. The dramatic phenotypic enhancement observed in Bif1; bif2 double mutants implies that bif1 plays an overlapping role with bif2 in the initiation of lateral organs during vegetative development. The phenotypic resemblance of Bif1 to bif2 mutants and the reduction of auxin transport in Bif1 mutants suggest that bif1 functions as a regulator of auxin transport in maize.

Heritability of skeleton abnormalities (lordosis, lack of operculum) in gilthead seabream ( Sparus aurata) supported by microsatellite family data

Body abnormalities constitute an important problem to fish aquaculture. Pigmentation, scale and skeleton abnormalities have been reported in different cultured fish species. Environmental and genetic factors or their interaction have been suggested to explain their origin. Gilthead seabream ( Sparus aurata) is one of the most important European cultured species. Lordosis and lack of operculum are common abnormalities in this species, and can reach frequency of 80% or more of commercial batches. In spite of an important body of data suggesting environmental factors related with their origin, scarce and not conclusive genetic data have been reported to date. In our study, a large number of families originating from the usual production process of a commercial farm were used to estimate the heritabilities of both characters. Two independent experiments were carried out for each abnormality. Nine hundred and ninety four (5.6% lordotics; 157 full-sib families; 6.3 offspring/family) and 808 (7.9% lacking operculum; 83 families; 9.7 offspring/family) individuals were used for lordosis and lacking operculum heritability estimations, respectively. The results obtained adjusting an animal model indicated non significant heritabilities for both characters (0.021 (s.e. 0.019) and 0.032 (s.e. 0.023) for lordosis and lack of operculum, respectively). The corresponding values when a threshold model was used, though higher (0.152 and 0.203, respectively), evidenced large standard errors (0.119 and 0.146, respectively) suggesting h 2 = 0 as the most confident hypothesis ( P = 0.838 and 0.766, respectively). A non-parametric permutation test was also applied to evaluate if more related individuals had a higher phenotypic resemblance. The results obtained suggested only a slight familiar association ( P < 0.05) when comparing individuals lacking operculum, but neither between lordotics nor between normal ones. These results suggest that most phenotypic variation observed for lordosis and lack of operculum in gilthead seabream is due to environmental factors.

Amplified 16S Ribosomal DNA Restriction Analysis for Identification of Avibacterium paragallinarum

A molecular technique based on the restriction fragment length polymorphism of the 16S ribosomal genes amplified by a polymerase chain reaction (PCR), referred to as amplified 16S ribosomal DNA restriction analysis (ARDRA), was designed to identify 19 Avibacterium paragallinarum strains isolated from infraorbital sinus and nasal turbinate bone samples of broiler chickens, breeders, and laying hens from different regions of Peru. The 16S rDNA was amplified by PCR using a pair of bacterial universal primers and restriction analysis of 16S rDNA sequences was done to select endonucleases with the highest number of cutting points inside the 16S rDNA. The DNA patterns with DdeI and RsaI endonucleases were identical for the 19 A. paragallinarum strains, but differed from those obtained for Ornithobacterium rhinotracheale, a bacterium with a high genetic and phenotypic resemblance to A. paragallinarum, as well as from Escherichia coli, a bacterium associated with infectious coryza. The ARDRA method could prove to be valuable for molecular identification of A. paragallinarum, a microorganism implicated in respiratory diseases in commercial birds.

Target regulation of V2R expression and functional maturation in vomeronasal sensory neurons in vitro

Vomeronasal receptors from the V1R and V2R gene families mediate the detection of chemical stimuli such as pheromones via the vomeronasal organ (VNO). The differential expression of vomeronasal receptors might contribute in part to a variety of pheromonal effects, which are different sexually, developmentally and even individually. However, little is known about the mechanisms controlling vomeronasal receptor expression. Cultured vomeronasal sensory neurons (VSNs) bear phenotypic resemblance to the intact VNO but they remain immature. Because indices of VSN maturation are increased by coculture with the target cells for VSNs, accessory olfactory bulb (AOB) neurons, AOB neurons may regulate vomeronasal receptor expression and functional maturation in VSNs. To test this hypothesis, we examined the expression of V2R-type vomeronasal receptors (VR1 and VR4) and chemosensory responsiveness in VNOs cocultured with AOB neurons. Immunoblot and immunocytochemical analysis revealed that the coculture of VNOs with AOB neurons resulted in a greater expression of VR1 and VR4 after 10 days than VNOs cultured alone. Moreover, calcium imaging analysis showed that cocultured VNOs responded to urine components applied iontophoretically into their cavities with a time course similar to the V2R expression, in contrast to singly cultured VNOs that displayed no response. These results demonstrate that AOB neurons induce the expression of vomeronasal receptors in VSNs, allowing them to function.

CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells

AbstractChronic lymphocytic leukemia (CLL) cells are thought to have diminished cell-cycling capacity, a view challenged by their phenotypic resemblance to activated human B lymphocytes. The present study addresses the cell-cycling status of CLL cells, focusing on those leukemic cells expressing CD38, a molecule involved in signaling and activation that also serves as a prognostic marker in this disease. CD38+ and CD38− members of individual CLL clones were analyzed for coexpression of molecules associated with cellular activation (CD27, CD62L, and CD69), cell-cycle entry (Ki-67), signaling (ZAP-70), and protection from apoptosis (telomerase and Bcl-2). Regardless of the size of the CD38+ fraction within a CLL clone, CD38+ subclones are markedly enriched for expression of Ki-67, ZAP-70, human telomerase reverse transcriptase, and telomerase activity. Although the percentage of cells (approximately 2%) entering the cell cycle as defined by Ki-67 expression is small, the absolute number within a clone can be sizeable and is contained primarily within the CD38+ fraction. Despite these activation/proliferation differences, both CD38+ and CD38− fractions have similar telomere lengths, suggesting that CD38 expression is dynamic and transient. These findings may help explain why high percentages of CD38+ cells within clones are associated with poor clinical outcome.

Proliferation and Expression of Progenitor and Mature Retinal Phenotypes in the Adult Mammalian Ciliary Body after Retinal Ganglion Cell Injury

Despite the identification of a small population of cells residing in the ciliary body (CB) of the adult mammalian eye that have the capacity to generate retina-like cells in vitro, their activity in vivo remains quiescent. The authors sought to identify whether the predictable and time-dependent death of retinal ganglion cells (RGCs) results in activation of progenitor-like cells within the CB. RGC injury was induced by optic nerve axotomy in adult mice. Thymidine-analogue lineage tracing and immunocytochemistry were used to identify dividing cells and the phenotype of newly generated progeny. Two populations of nestin-expressing cells are present in the CB of the uninjured eye. One population resides in periendothelial cells of blood vessels, and a second resides in the ciliary epithelium. Axotomy increases proliferation in the CB, a response that begins before the onset of RGC death and continues during a time that corresponds with the peak in RGC death. In addition, a subpopulation of nestin-positive cells in the CB upregulates the homeodomain protein Chx10. Finally, recoverin, the expression of which is normally restricted to photoreceptors and bipolar cells of the retina, is upregulated in the CB in a manner that is independent of proliferation. Together, these results suggest that progenitorlike cells of the CB respond to cues associated with the loss of a single retinal cell type and that a subpopulation of those cells may differentiate into a cell that bears phenotypic resemblance to those seen in the retina.

Coping with habitat heterogeneity: the story of Mediterranean blue tits

A prerequisite for understanding adaptation is to understand how populations respond to environmental heterogeneity. We chose the blue tit Cyanistes caeruleus and Mediterranean habitat mosaics which exhibit a large diversity of habitats for analysing the effects of environmental heterogeneity on phenotypic variation. Three main factors of heterogeneity have been considered: (1) whether dominant tree species are deciduous or evergreen, (2) the geographic configuration of habitats and landscapes, and (3) the degree of infestation by parasites, which considerably varies in space. Several study sites equipped with nest-boxes and traps for collecting the droppings of caterpillars falling from the leaves of trees have been monitored over several decades in a series of habitats in mainland and insular (Corsica) landscapes. Depending on the geographic configuration of habitat patches within landscapes, the large phenotypic variation observed in many demographic, morphometric and behavioural traits has been shown to result either from a plastic response to habitat variation or from genetically determined specialisation to local habitats. Blue tits in deciduous habitats started to breed ca. 1 month earlier than in evergreen habitats, but patterns differed between the mainland and Corsica. On the mainland, populations may be locally maladapted because of gene flow across habitat patches, which results in a low supply/demand ratio of food, poor breeding performance and a source–sink population structure. In Corsica, higher phenotypic variation resulted from lower dispersal ranges in islands, a component of the insular syndrome. Genetically-based habitat-specific specialisation to local habitats on this island is a demonstration that adaptive responses of suites of life history traits to habitat-specific selection regimes may operate on a scale which is much smaller than the scale of potential dispersal and gene flow. Adaptive responses of blue tits to two constraints, i.e. high levels of parasitism and low amounts of food, have been studied in detail. The very small amount of measured genetic divergence between populations contrasts with the large inter-population phenotypic variation which is observed in many traits. This is one more example that natural selection can produce rapid and sometimes strongly adaptive morphological divergence in the absence of discernable differentiation at neutral DNA loci, and that weak genetic differentiation does not necessarily mean phenotypic resemblance.

Characterization of lamin Mutation Phenotypes in Drosophila and Comparison to Human Laminopathies

Lamins are intermediate filament proteins that make up the nuclear lamina, a matrix underlying the nuclear membrane in all metazoan cells that is important for nuclear form and function. Vertebrate A-type lamins are expressed in differentiating cells, while B-type lamins are expressed ubiquitously. Drosophila has two lamin genes that are expressed in A- and B-type patterns, and it is assumed that similarly expressed lamins perform similar functions. However, Drosophila and vertebrate lamins are not orthologous, and their expression patterns evolved independently. It is therefore of interest to examine the effects of mutations in lamin genes. Mutations in the mammalian lamin A/C gene cause a range of diseases, collectively called laminopathies, that include muscular dystrophies and premature aging disorders. We compared the sequences of lamin genes from different species, and we have characterized larval and adult phenotypes in Drosophila bearing mutations in the lam gene that is expressed in the B-type pattern. Larvae move less and show subtle muscle defects, and surviving lam adults are flightless and walk like aged wild-type flies, suggesting that lam phenotypes might result from neuromuscular defects, premature aging, or both. The resemblance of Drosophila lam phenotypes to human laminopathies suggests that some lamin functions may be performed by differently expressed genes in flies and mammals. Such still-unknown functions thus would not be dependent on lamin gene expression pattern, suggesting the presence of other lamin functions that are expression dependent. Our results illustrate a complex interplay between lamin gene expression and function through evolution.

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

NK cells and gammadelta T cells are distinct subsets of lymphocytes that contextually share multiple phenotypic and functional characteristics. However, the acquisition and the extent of these similarities remain poorly understood. Here, using T cell receptor delta locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) reporter mice, we show that germ-line transcription of Tcrd occurs in all maturing NK cells. We also describe a population of mouse NK-like cells that are indistinguishable from "bona fide" NK cells using standard protocols. Requirements for V(D)J recombination and a functional thymus, along with very low-level expression of surface TCRgammadelta but high intracellular CD3, define these cells as gammadelta T cells. "NK-like gammadelta T cells" are CD127+, have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-gamma in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like gammadelta T cells is a source of experimental ambiguity in studies bridging NK and T cell biology, such as those on thymic NK cell development. Instead, it ascribes chronic TCRgammadelta engagement as a means of acquiring NK-like function.

Hyperbaric oxygen therapy of angiopathic changes in patients with inherited gene imbalance

Phenotype match inherited by genes is in most cases present in monozygotic twins. Their phenotypic resemblance is unfortunately characterized by strong susceptibility for the development of chronic non-infectious diseases. One of the most common non-infectious chronic diseases that are phenotipically represented in twins is diabetes mellitus. Genetic imbalance is, in most cases, placed in 2, 3, 7, 8, 11, 12, 19 and 20 chromosomal pair of the human genome. This study describes a pair of monozygotic twins, aged 54, who were diagnosed for diabetes type 2 ten years earlier. The first patient had trophic changes of muscles and skin tissues of the lower limb, and a necrotic wound on his right leg tibial region with the claudication distance of 50 m. After arteriography, he was referred by a vascular surgeon for hyperbaric oxygen therapy (HBO). HBO protocol implied 70 min. application of 100% oxygen at 2.5 absolute atmospheres. After the first series of HBO therapies consisting of 20 HBO treatments, claudication was eliminated and the necrotic wound healed. Next, surgical aortofemoral bypass was done. During the second HBO treatment, his monozygotic twin brother presented with angiopathic changes due to diabetes. In both patients, biochemical parameters corresponded to the expected level for diabetes type 2 imbalance, and the localization of the chromosomal defect (placed on 3, 11 and 19 chromosomal pair) was also in accordance with the respective disorder. After they were included into next 10 HBO treatments, Doppler imaging of the major arteries of limbs revealed normal findings. Identical genetic impairment in monozygotic twins can lead to identical somatic changes with resultant consequences. HBO treatment of such patients associated with other therapeutic procedures (conducted by diabetologist, vascular surgeon and physiatrist) can postpone or prevent irreversible changes occurring due to blood vessel disorders.

Intrinsic Parent‐Offspring Correlation in Inbreeding Level in a Song Sparrow (Melospiza melodia) Population Open to Immigration

The extent to which offspring resemble their parents in genotype and phenotype underpins patterns of genetic and phenotypic variation, selection, and evolution in natural populations. Genetic and phenotypic resemblance can clearly result from additive genetic variance and can be shaped by nongenetic parental and common environmental influences. In contrast, there is no straightforward expectation that inbreeding coefficient (f), a nonadditive component of genetic "quality," should be correlated across parents and offspring in sexually reproducing species or consequently cause resemblance across generations. Here, we report a significant parent f-offspring f correlation within a free-living pedigreed population of song sparrows (Melospiza melodia) on Mandarte Island, Canada. Across 15 years, relatively inbred parents had relatively inbred offspring on average. We show that rather than requiring nonrandom pairing with respect to f and kinship, parent f-offspring f correlations arise as an intrinsic consequence of random pairing within Mandarte's open population, where immigrants interbreed with Mandarte-hatched natives. However, on Mandarte, parent f-offspring f correlations may have been exacerbated because relatively inbred individuals paired with more closely related mates than expected by chance. Such intrinsic parent f-offspring f correlations have major implications for the understanding of resemblance, selection, and evolution in natural populations.

Genetic Analysis of Sensation Seeking with an Extended Twin Design

The heritability of sensation seeking is investigated in an extended twin design, including mono- and dizygotic twins and their siblings. Besides a comparison of the phenotypic resemblance between monozygotic twins and dizygotic twins, the design allows for an explicit test of the assumption that results from twins may be generalized to the singleton population. Secondly, the design offers the opportunity to investigate to what extent the influence of common environment is the same for males and females and for twins and siblings, i.e. allowing for explicit tests of a special twin environment and of a sex-specific common environment. The results indicate that individual variation in sensation seeking is heritable, with few differences between males and females in heritability estimates for the sensation seeking dimensions. In contrast to prior studies, evidence is found for common environmental influences for thrill and adventure seeking in males, and experience seeking and boredom susceptibility in females. Evidence for a special twin environment was limited to boredom susceptibility in females.

An Organized Medullary Epithelial Structure in the Normal Thymus Expresses Molecules of Respiratory Epithelium and Resembles the Epithelial Thymic Rudiment of Nude Mice

The expression of tissue-specific Ags (TSA) within the thymic environment has emerged as an important contribution to the establishment of self-tolerance. The mechanistic basis for this property is poorly understood. One model has proposed stochastic derepression of gene expression by mature medullary epithelial cells, whereas another model has suggested that this property of thymic epithelial cells reflects transcriptional activity during their differentiation. Most of the analyses of thymic TSA expression have been done with populations of dissociated thymic epithelial cells; therefore, there is little information regarding the spatial pattern of TSA expression within the thymus. We have evaluated a subset of thymic epithelial cells in the murine thymus that display several unique features. First, within the normal thymus, they form cysts that express several TSA of respiratory epithelium and exhibit some morphological features consistent with respiratory epithelium. These cells also display a phenotypic profile that has been proposed for immature thymic epithelium. The cystic epithelia in the normal thymus and in the nude thymic rudiment are phenotypically very similar, suggesting that they may have a similar developmental program. The coordinated expression of respiratory TSA by an organized subset of thymic epithelial cells and the phenotypic resemblance of these cells to progenitor cells seem consistent with a developmental basis for TSA expression by thymic epithelial cells. Finally, epitopes that define thymic epithelial heterogeneity are reciprocally expressed by respiratory epithelium, which raises interesting questions regarding the developmental relationship of different endodermal derivatives.

Exploitation of a specialized mutualism by a deceptive orchid

Plants that lack floral rewards may nevertheless attract pollinators through mimetic resemblance to the flowers of co-occurring rewarding plants. We show how a deceptive orchid (Disa nivea) successfully exploits a reciprocally specialized mutualism between a nectar-producing plant (Zaluzianskya microsiphon) and its long-proboscid fly pollinator (Prosoeca ganglbaueri). Disa nivea is a rare southern African orchid known only from habitats that support large populations of Z. microsiphon, which it closely resembles in both general morphology and floral spectral reflectance. Significant covariation in floral traits of Z. microsiphon and D. nivea was detected among populations. Where mimics are uncommon, flies do not appear to discriminate between the flowers of the two species. Pollination success in D. nivea was much higher at a site with abundant Z. microsiphon plants than at a site where Z. microsiphon was rare. Exploitation of a highly specialized mutualism appears to demand a high degree of phenotypic resemblance to a rewarding model by a deceptive mimic, as exemplified by D. nivea. The majority of deceptive orchids, on the other hand, exploit relatively generalized pollination systems and thus require only a vague resemblance to rewarding plants in the community in order to attract pollinators.

Late Pleistocene/Holocene craniofacial morphology in Mesoamerican Paleoindians: Implications for the peopling of the New World

Several studies on craniofacial morphology showed that most Paleoindians, who were the first settlers of the New World, clearly differ from modern Amerindians and East Asians, their supposed descendants and sister group, respectively. Here we present new evidence supporting this view from the Late Pleistocene/Early Holocene horizon from Mexico, as well as from the most complete set of dated Paleoindian remains. We analyzed the phenotypic resemblance of early Mexicans with other South Paleoamerican and modern human series. Two independent approaches to the data were used. In the first case, individual specimens were tested for morphological similarity with a set of modern reference samples. In the second analysis, Mexican specimens were treated as a sample in order to compute minimum genetic distances. Results from both approaches tend to associate early Mexican skulls with Paleoindians from Brazil, an Archaic sample from Colombia, and several circum-Pacific populations. These results give support to a model in which morphologically generalized groups of non-Northeast Asian descent (the so-called Paleoamericans) entered the continent first, and then dispersed from North to South America through Central America. The large geographic dispersal of Paleoamericans, and their presence in Mexico in the Early Holocene, raise new issues about the continent's settlement scenario.

Gamete donation in a system of need-adjusted reciprocity

A new paradigm to collect and allocate donor gametes is proposed. In the system, called indirect mirror exchange, the partner of the person who needs donor gametes, donates in exchange for bonus points that are awarded to the infertile person. All candidate recipients of donor gametes are ranked on a waiting list and receive points according to waiting time, medical urgency, phenotypic resemblance and contribution. According to the principle of fairness, persons who benefit from a system are obliged to contribute their share. However, strict reciprocity is rejected as unfair. A contribution by the couple is thus not a necessary condition for access to the waiting list. The system of reciprocity is adjusted by taking account of need considerations. The number of bonus points awarded to contributors should be high enough to move them to the front section of the waiting list.

Ptc1 heterozygous knockout mice as a model of multi-organ tumorigenesis

Mutations in the Ptc1 gene are responsible for basal cell nevus (BCN) syndrome, and are commonly found in sporadic basal cell carcinomas (BCC) and in medulloblastoma (MB). Ptc1 hemizygosity in mice underlies this model's susceptibility to multi-organ tumorigenesis. Similar to BCN syndrome patients, the Ptc1 mouse model is characterized by tumor predisposition and radiation hypersensitivity. Ptc1 +/− mice develop spontaneous rhabdomyosarcoma (RMS) and medulloblastoma (MB), as well as BCC following radiation exposure. The close phenotypic resemblance to the human disease makes these mice a unique preclinical model to test chemopreventive and therapeutic interventions.