LacZ Reporter Mice Research Articles

Neuron-specific recombination by Cre recombinase inserted into the murine tau locus

To determine the neuronal function of genes in vivo, the neuron-specific deletion of a target gene in animals is required. Tau, a microtubule-associated protein, is expressed abundantly in neurons but scarcely in glias and other tissues. Therefore, to generate mice that express Cre recombinase in neurons, we inserted Cre recombinase into the tau locus. By crossing these tau-Cre mice with ROSA26 lacZ reporter mice, we observed Cre recombinase activity in the neurons from most of the central nervous system, but not in glias nor in non-neuronal tissues. This neuronal-specific activity appeared during embryogenesis. We further crossed tau-Cre mice with rab8 ‘floxed’ mice, and showed that the recombination was nearly complete in the brain, but incomplete or non-detectable in other tissues. Thus, tau-Cre knockin mouse is a useful tool for studying the neuronal function of a gene in vivo.

Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus

Establishment of neuronal diversity is a central topic in developmental neurobiology. Prior studies implicated Pitx2, a paired-like homeodomain transcription factor, in mouse subthalamic nucleus neuronal development, but precise stages of neuronal differentiation affected (migration, axon outgrowth, fate specification) and underlying mechanisms were unknown. Here we report lineage tracing experiments using Pitx2 cre/+ , Pitx2 cre/null , and conditional nuclear lacZ reporter mice to track embryonic Pitx2 expressing neurons. Migration of subthalamic nucleus and hypothalamic neurons was severely arrested in Pitx2 cre/null embryos, and subclasses of subthalamic nucleus neurons identified by Lmx1b, Foxp1, and Foxp2-gene expression revealed differing sensitivities to Pitx2 dosage. Interestingly, embryonic subthalamic nucleus development was unaffected in Lmx1b null mice, suggesting that Pitx2 and Lmx1b act via independent genetic pathways. These data provide the first direct evidence for Pitx2-dependent neuronal migration in the developing hypothalamus, and demonstrate that complex transcriptional networks regulate regional specialization of distinct hypothalamic and subthalamic nucleus neurons.

Incudomalleal joint formation: the roles of apoptosis, migration and downregulation

BackgroundThe middle ear of mammals is composed of three endochondrial ossicles, the stapes, incus and malleus. Joints link the malleus to the incus and the incus to the stapes. In the mouse the first arch derived malleus and incus are formed from a single Sox9 and Type II collagen expressing condensation that later subdivides to give rise to two separate ossicles. In contrast the stapes forms from a separate condensation derived from the second branchial arch. Fusion of the malleus and incus is observed in a number of human syndromes and results in conductive hearing loss. Understanding how this joint forms during normal development is thus an important step in furthering our understanding of such defects.ResultsWe show that the developing incudomalleal joint is characterised by a lack of proliferation and discrete areas of apoptosis. Apoptosis has been suggested to aid in the removal of pre-cartilaginous cells from the joint region, allowing for the physical separation of the cartilaginous elements, however, we show that joint initiation is unaffected by blocking apoptosis. There is also no evidence of cell migration out of the presumptive joint region, as observed by labelling of joint and ossicle cells in culture. Using Type II collagen lacZ reporter mice, however, it is evident that cells in the presumptive joint region remain in place and downregulate cartilage markers.ConclusionThe malleus and incus first appear as a single united condensation expressing early cartilage markers. The incudomalleal joint region forms by cells in the presumptive joint region switching off cartilage markers and turning on joint markers. Failure in this process may result in fusion of this joint, as observed in human syndromes such as Branchio-Oto-Renal Syndrome or Treacher Collins Syndrome.

Expression of G-CSF Receptor during Embryonic Development in a Csf3r-Cre Knock-In Mouse Model.

G-CSF is the major regulator of neutrophil development and controls the proliferation, differentiation and survival of myeloid progenitors in both steady state and “emergency” granulopoiesis. More recently however, novel activities of the G-CSF/G-CSF receptor (CSF3R) axis have been suggested, especially after severe forms of tissue damage. For instance, upon myocardial infarction, G-CSF was shown to protect cardiomyocytes from apoptosis, reducing the extent of myocardial damage. Likewise, in ischemic stroke models, G-CSF treatment reduced infarct volumes by promoting neuronal survival and differentiation of neural stem cells in the brain. Finally, G-CSF has been suggested to promote hepatic regeneration after severe liver damage by directly stimulating the proliferation of oval cells. To study whether and to what extent CSF3R expression in damaged tissues reflects reactivation of a normal development program, we generated a csf3r-Cre knock-in model. To this end, the csf3r locus was targeted with a construct containing the cre gene and a puromycin selection cassette flanked by a 2.7 kb fragment of the csf3r 5′UTR and a 4 kb fragment directly downstream of the initiation codon of csf3r. Correct insertion of the cre gene was confirmed by Southern blotting and sequence analysis and subsequent crossing with FLP deleter mice resulted in successful germ line transmission and deletion of the puromycin cassette. These mice were crossed with the R26R LacZ reporter mouse and β-galactosidase (β-gal) activity was examined by FACS and histochemical analysis. At E9.5, no β-gal activity was detected, indicating that csf3r is not expressed at that stage of development. In contrast, in E12.5 embryos, β-gal staining was observed in fetal liver, heart, kidney, brain and intestine. Analysis of adult tissues showed that cardiomyocytes were β-gal positive in a mosaic pattern. A similar mosaicism was observed in liver, kidney and the intestines. In liver both hepatocytes and vascular endothelial cells stained positive, whereas in the kidney β-gal staining was detected in vascular endothelium, glomeruli and afferent and efferent vessels. In ileum and colon, β-gal activity was mainly seen in the stem and progenitor cell-containing crypts and the developing progeny migrating upwards along the villus. In bone marrow, high levels (>40%) of β-gal activity were detected in Gr1+ and CD11b+ myeloid cells, CD19+ (B) and CD3ε+ (T) lymphoid cells, NK cells and CD11c+ dendritic cells, indicating that G-CSFR was expressed in a common progenitor of these cell types. In agreement with this, β-gal activity was also detected in the primitive LSK population. In conclusion, our data indicate that CSF3R is expressed in both hematopoietic and multiple non-hematopoietic organs from embryonic development stage E12.5 onward. This may have important ramifications for a more wide-spread application of G-CSF in tissue regeneration.

Regulation of MMP-2 Gene Transcription in Dermal Wounds

Matrix metalloproteinase-2 (MMP-2, gelatinase A) plays an essential role in angiogenesis, inflammation, and fibrosis. These processes are critical for wound healing and accordingly elevated levels of MMP-2 expression have been detected after skin injury. Our goal was to investigate the transcriptional activation of the MMP-2 gene in a model of skin injury by using two different MMP-2/LacZ-reporter mice. Upon skin injury MMP-2 expression was upregulated, whereas tissue from normal skin stained negative except for occasional macrophages, sweat glands, and hair follicles. Skin injury also activated MMP-2 proteolytic activity and reporter gene expression. We demonstrate that MMP-2 regulatory sequences -1686/+423 drive appropriate injury-induced MMP-2-promoter activation. Reporter gene expression was predominantly detectable in endothelial cells and in macrophages. Deletion of the 5' responsive element, denoted RE-1, residing at -1241/+423 bp of the regulatory sequence led to abrogated MMP-2 transcription in vivo. The findings define a crucial role for the enhancer element RE-1 in injury-induced MMP-2 transcription of the skin.

Keratin Expression Provides Novel Insight into the Morphogenesis and Function of the Companion Layer in Hair Follicles

Hair follicles cycle between stages of growth (anagen) and metabolic quiescence (telogen) throughout life. In mature follicles, transition from telogen back into anagen involves the activation, proliferation, and differentiation of epithelial stem cells located in the bulge, a specialization of the outer root sheath. Recent studies identified keratin 6a (K6a) transcripts as enriched in bulge epithelial stem cells in mouse skin. We used messenger RNA probes, antibodies, a LacZ reporter mouse model, and whole-mount staining assays to investigate the regulation of mK6a during mouse postnatal hair cycling, and compare it to mK75, a companion layer (Cl) marker. We find that mK75 regulation parallels that of inner root sheath (IRS) markers, with expression onset at anagen IIIa above the new hair bulb and subsequent spreading towards the bulge. Although also occurring in the Cl, mK6a expression begins at anagen IIIb in differentiating cells located proximal to the bulge, and subsequently spreads towards the hair bulb. mK6a and mK75 thus exhibit temporally distinct, and spatially opposed, expression patterns in the Cl during postnatal anagen. These findings provide novel insight into the morphogenesis and properties of the Cl, and raise the distinct possibility that it is an integral part of the IRS compartment.

The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field

The vertebrate heart arises from the fusion of bilateral regions of anterior mesoderm to form a linear heart tube. Recent studies in mouse and chick have demonstrated that a second cardiac progenitor population, known as the anterior or secondary heart field, is progressively added to the heart at the time of cardiac looping. While it is clear that this second field contributes to the myocardium, its precise boundaries, other lineages derived from this population, and its contributions to the postnatal heart remain unclear. In this study, we used regulatory elements from the mouse mef2c gene to direct the expression of Cre recombinase exclusively in the anterior heart field and its derivatives in transgenic mice. By crossing these mice, termed mef2c-AHF-Cre, to Cre-dependent lacZ reporter mice, we generated a fate map of the embryonic, fetal, and postnatal heart. These studies show that the endothelial and myocardial components of the outflow tract, right ventricle, and ventricular septum are derivatives of mef2c-AHF-Cre expressing cells within the anterior heart field and its derivatives. These studies also show that the atria, epicardium, coronary vessels, and the majority of outflow tract smooth muscle are not derived from this anterior heart field population. Furthermore, a transgene marker specific for the anterior heart field is expressed in the common ventricular chamber in mef2c mutant mice, suggesting that the cardiac looping defect in these mice is not due to a failure in anterior heart field addition to the heart. Finally, the Cre transgenic mice described here will be a crucial tool for conditional gene inactivation exclusively in the anterior heart field and its derivatives.

Coplanar Polychlorinated Biphenyls Activate the Aryl Hydrocarbon Receptor in Developing Tissues of Two TCDD-Responsive lacZ Mouse Lines

In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can have an immediate impact on developmental processes that then lead to long-term deficits in function. To define the specific tissues affected by TCDD during development, we developed a lacZ-reporter gene mouse model driven by activation of the aryl hydrocarbon receptor (AhR). Exposure to TCDD on gestational day (GD) 14 results in strong activation of the lacZ transgene in numerous tissues including fore and hind paws, ear, and genital tubercle. Experiments were conducted to examine the ability of alternative AhR ligands to activate our model system. The coplanar polychlorinated biphenyl congeners 3,4,5,3',4'-pentachlorobiphenyl (PCB126) and 3,4,3',4'-tetrachlorobiphenyl (PCB77) both induced staining in fetal tissues identical to that observed following TCDD exposure. Exposure of fetuses to the PCB mixture Aroclor 1254 and the non-coplanar congener 2,3,6,2',5'-pentachlorobiphenyl (PCB95) did not result in any activation of the lacZ transgene. In addition to the testing of alternative ligands, another line of reporter mice was generated to determine the potential influence of the site of insertion of the lacZ transgene on the reported observations. Both TCDD and the coplanar PCBs induced a similar pattern of staining in the new line as compared to that observed in the original lacZ reporter mouse line. The ability of AhR ligands, other than TCDD, to activate the AhR-mediated transgene, in combination with the insertion-site independence of the response, strengthens the data previously derived from this model and increases the utility of this system for investigations examining AhR-mediated events during development.

Regulation of anxiety and initiation of sexual behavior by CREB in the nucleus accumbens

Sexual deficits and other behavioral disturbances such as anxiety-like behaviors can be observed in animals that have undergone social isolation, especially in species having important social interactions. Using a model of protracted social isolation in adult rats, we observed increased anxiety-like behavior and deficits in both the latency to initiate sexual behavior and the latency to ejaculate. We show, using transgenic cAMP response element (CRE)-LacZ reporter mice, that protracted social isolation also reduces CRE-dependent transcription within the nucleus accumbens. This decrease in CRE-dependent transcription can be mimicked in nonisolated animals by local viral gene transfer of a dominant negative mutant of CRE-binding protein (CREB). We previously showed that this manipulation increases anxiety-like behavior. We show here that it also impairs initiation of sexual behavior in nonisolated animals, a deficit that can be corrected by anxiolytic drug treatment. This local reduction in CREB activity, however, has no influence on ejaculation parameters. Reciprocally, we used the viral transgenic approach to overexpress CREB in the nucleus accumbens of isolated animals. We show that this local increase in CREB activity completely rescued the anxiety phenotype of the isolated animals, as well as their deficit in initiating sexual behavior, but failed to rescue the deficit in ejaculation. Our data suggest a role for the nucleus accumbens in anxiety responses and in specific aspects of sexual behavior. The results also provide insight into the molecular mechanisms by which social interactions affect brain plasticity and behavior.

Vascular Endothelial Cadherin-Expressing Cells Involved in Both Developmental and Adult Neovascularization.

Vessel formation, including vasculogenesis and angiogenesis, is thought to be directly mediated by adhesive molecules between vascular endothelial cells and adjacent cells. Vascular endothelial cadherin (VE-cadherin, CD144) is a adhesive molecule exclusively expressed in adherens junctions of cultured endothelial cells. VE-cadherin transcripts have been detected at first in mesodermal cells. However, no work has focused on which cell type expresses VE-cadherin during vessel formation and after vessel stabilization. To monitor VE-cadherin in vivo, we generated transgenic mice expressing a VE-cadherin promoter-driven Cre (VE-cad-Cre). By crossing VE-cad-Cre with loxP-based EGFP reporter mice (CAG-CAT-EGFP) and LacZ reporter mice (cAct-XstopX-LacZ), we obtained two double transgenic mice; one expressing EGFP (VE/EG) another expressing LacZ (VE/Z) dependently upon Cre driven by VE-cadherin promoter. Both reporter expression was increased in developing vasculature during embryogenesis, while it was decreased in postnatal vessel maturation. Intriguingly, LacZ reporter was found in the budding cells and lining cells of the dorsal aorta in the aorta-gonad-mesonephros region, suggesting that VE-cadherin-expressing cells belongs to hemangioblasts. Consistently, although VE-cadherin and its mRNA was detected in vasculature by immunohistochemistry and in situ hybridization, respectively, during embryogenesis, it was not detected in maturated vessels. These results indicated that VE-cadherin promoter activity reflects the endogeneous VE-cadherin expression and that VE-cadherin promoter is activated during developmental vasculogenesis and angiogenesis. To test whether the VE-cadherin promoter is re-activated in postnatal neovascularization, we used two models; a VEGF-induced cornea angiogenesis model and a myocardial ischemia model. VEGF implanted in the VE/EG eyes promoted the neovascularization visualized by EGFP expression. Myocardial ischemia in which the coronary artery was banded triggered the VE-cadherin promoter, thereby inducing reporter expression in vascular cells (endothelial cells and mural cells) of undamaged region and in infiltrated cells of damaged region. Furthermore, by flow cytometric analyses, we confirmed that myocardial ischemia re-activated the VE-cadherin promoter of both bone marrow cells and peripheral blood cells, as indicated by the remarkable increase of EGFP-positive cells. These data show that the VE-cadherin promoter is re-activated in pre-existing vascular cells and infiltrated cells during adult neovascularization. Collectively, VE-cadherin-expressing cells participates in both developmental and postnatal vasulogenesis and angiogenesis.

Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus.

Catecholaminergic neurons are affected in several neurological and psychiatric diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase from the 3'-untranslated region of the endogenous Th gene by means of an internal ribosomal entry sequence (IRES). The resulting Cre expression matches the normal pattern of TH expression, while the pattern and level of TH are not altered in the knockin mouse. Crossings with two different LacZ reporter mice demonstrated Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ was found in some unexpected cell populations (including oocytes), indicating recombination due to transient developmental TH expression. Our novel knockin mouse can be used for generation of tissue-specific or general knockouts (depending on scheme of crossing) in mice carrying genes flanked by loxP sites. This knockin mouse can also be used for tracing cell lineages expressing TH during development.

Mapping oxytocin receptor gene expression in the mouse brain and mammary gland using an oxytocin receptor–LacZ reporter mouse

The hypothalamic nonapeptide oxytocin (OT) has an established role as a circulating hormone but can also act as a neurotransmitter and as a neuromodulator by interacting with its central OT receptor (OTR). To understand the role of the OTR in the mouse brain we investigated the expression of the OTR gene at the cellular level. We targeted the lacZ reporter gene to the OTR gene locus downstream of the endogenous OTR regulatory elements. Using lactating mouse mammary gland as a control for OTR promoter directed specificity of lacZ gene expression, X-gal histochemistry on tissue sections confirmed that gene expression was restricted to the myoepithelial cells. We also identified for the first time in mice the expression of the OTR gene in neighbouring adipocytes. Further, investigation in the mouse brain identified numerous nuclei containing neurons expressing the OTR gene. Whilst some of these regions had been described for rat or sheep, the OTR-LacZ reporter mouse enabled the identification of novel sites of central OTR gene expression. These regions include the accessory olfactory bulb, the medial septal nucleus, the posterolateral cortical amygdala nucleus, the posterior aspect of the basomedial amygdala nucleus, the medial part of the supramammillary nucleus, the dorsotuberomammillary nucleus, the medial and lateral entorhinal cortices, as well as specific dorsal tegmental, vestibular, spinal trigeminal, and solitary tract subnuclei. By mapping the distribution of OTR gene expression, depicted through histochemical detection of β-galactosidase, we were able to identify single OTR gene expressing neurons and small neuron clusters that would have remained undetected by conventional approaches. These novel sites of OTR gene expression suggest additional functions of the oxytocinergic system in the mouse. These results lay the foundation for future investigation into the neural role of the OTR and provide a useful model for further study of oxytocin functions in the mouse.

LacZ expression in Fut2-LacZ reporter mice reveals estrogen-regulated endocervical glandular expression during estrous cycle, hormone replacement, and pregnancy.

The secretor gene (FUT2) encodes an alpha(1,2)fucosyltransferase (E.C. 2.4.1.69) that elaborates alpha(1,2)fucose residues on mucosal epithelium and secreted mucins. Though uterine alpha(1,2)fucosylated glycans have been proposed to be involved in embryo adhesion, mice with a homozygous null mutation of Fut2 displayed normal fertility. To help develop alternative hypotheses for function, the cell type and regulation of Fut2 expression during the estrous cycle, hormone replacement, and pregnancy was examined in Fut2-LacZ reporter mice containing targeted replacement of Fut2 with bacterial lacZ. LacZ expression in the reproductive tract of Fut2-LacZ mice is most prominent in the glandular epithelium of the endocervix during estrus and pregnancy. Nuclear LacZ expression identifies cell-specific expression of Fut2 in mucus-secreting cells of the endocervix, uterine glands, foveolar pit and chief cells of the stomach, and goblet cells of the colon. In ovariectomized Fut2-LacZ mice, estradiol treatment stimulates X-gal staining in endocervix and uterus but does not affect expression in stomach and colon. Northern blot analysis in wild-type mice shows 15-fold elevations of Fut2 steady-state mRNA with estradiol treatment, whereas Fut1 varies little. Fut2 levels in the glandular stomach and distal colon remain constant, and uterine Fut2 levels vary eightfold during the estrous cycle. These data represent the first demonstration of a glycosyltransferase gene under tissue-specific hormonal regulation in a LacZ reporter mouse model. Endocervical expression of Fut2 in estrus and pregnancy may modify cervical mucus barrier properties from microbial infection analogous to the potential role of mucosal glycans in humans.

Spatiotemporal transcription of connexin45 during brain development results in neuronal expression in adult mice

Characterization of the expression pattern of connexins in neural tissue is a necessary prerequisite for understanding the functional relevance of the corresponding gap junction channels in brain. Here we describe the cell type-specific expression of connexin45 in the CNS and the spatiotemporal expression pattern from embryonic day 19.5 to adult brain using a recently described connexin45 LacZ-reporter mouse. The connexin45 gene is highly expressed during embryogenesis and up to 2 weeks after birth in nearly all brain regions. Afterward its expression is restricted to the thalamus, the CA3 region of hippocampus and the cerebellum. In adult mouse brain, the pattern of LacZ-staining in combination with the analysis of different neuronal and glial marker proteins strongly suggests that connexin45 is expressed in neurons, but presumably not in astrocytes or mature oligodendrocytes. Expression of the LacZ/connexin45 reporter gene in subsets of neurons, such as cerebral cortical, hippocampal and thalamic neurons as well as basket and stellate cells of cerebellum should be corroborated by functional investigations of connexin45 protein in electrical synapses. Based on its expression pattern during development, we suggest that the connexin45-containing gap junction channels have a rather ubiquitous role during brain development and may contribute to functional specification in certain subsets of neurons in the adult brain.

A novel LacZ reporter mouse reveals complex regulation of the progesterone receptor promoter during mammary gland development.

To further our understanding of progesterone (P) as an endocrine mammogen, a PR(lacz) knockin mouse was generated in which the endogenous progesterone receptor (PR) promoter directly regulated lacZ reporter expression. The PR(lacz) mouse revealed PR promoter activity was restricted to the epithelial compartment during the prenatal and postnatal stages of mammary gland development. At puberty, PR promoter activity was unexpectedly robust and restricted to the body cells within the terminal end buds and to the luminal epithelial cells in the subtending ducts. In the adult, the preferential localization of PR(lacz) positive cells to the distal regions of ductal side branches provided a cellular context to the recognized mandatory role of P in ductal side-branching, and segregation of these cells from cells that undergo proliferation supported an intraepithelial paracrine mode of action for P in branching morphogenesis. Toward the end of pregnancy, the PR(lacz) mouse disclosed a progressive attenuation in PR promoter activity, supporting the postulate that the preparturient removal of the proliferative signal of P is a prerequisite for the emergence of a functional lactating mammary gland. The data suggest that PR expression before pregnancy is to ensure the specification and spatial organization of ductal and alveolar progenitor cell lineages, whereas abrogation of PR expression before lactation is required to enable terminal differentiation of the mammary gland.

413. Development of a LacZ Reporter Mouse to Evaluate Spliceosome Mediated RNA Trans-Spicing In Vivo

413. Development of a LacZ Reporter Mouse to Evaluate Spliceosome Mediated RNA Trans-Spicing In Vivo

Timing the doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene.

We have developed a transgenic mouse expressing the Cre recombinase under control of a tetracycline-responsive promoter. Using a CamKIIalpha-driven tTA transgenic strain and a lacZ reporter mouse, we obtained the expected neuronal pattern of recombination in the olfactory lobe, cortex, striatum, hippocampus and Purkinje cells. Moreover, recombination can be completely abolished by feeding the mice doxycycline in their drinking water. We also show that it is possible to get a different pattern of recombination by changing the timing of the doxycycline-mediated shutdown of Cre expression. By starting the doxycycline treatment at birth, we restrict recombination to striatum only. This approach should be applicable to other inducible transgenic strains, thus increasing the number of available tissue-specific patterns for conditional knockouts. Also, our tetO-Cre transgene can be combined with any of the increasing number of tetracycline transactivator transgenic strains to direct specifically inducible genomic recombination to several areas of the brain.

Improved detection reliability of beta-galactosidase in histological preparations.

BioTechniquesVol. 27, No. 3 BenchmarksOpen AccessImproved Detection Reliability of β-Galactosidase in Histological PreparationsGang Cheng, Robert P. Thompson & Robert G. GourdieGang Cheng*Address correspondence to Dr. Gang Cheng, Department of Anatomy and Cell Biology, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425, USA. Internet: E-mail Address: chengg@musc.eduMedical University of South Carolina, Charleston, SC, USASearch for more papers by this author, Robert P. ThompsonMedical University of South Carolina, Charleston, SC, USASearch for more papers by this author & Robert G. GourdieMedical University of South Carolina, Charleston, SC, USASearch for more papers by this authorPublished Online:22 Aug 2018https://doi.org/10.2144/99273bm08AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail FiguresReferencesRelatedDetailsCited ByAnalysis of Gene Expression Using lacZ Reporter Mouse Lines20 February 2021Preservation of large-scale chromatin structure in FISH experiments22 November 2006 | Chromosoma, Vol. 116, No. 2Combined Angiopoietin-1 and vascular endothelial growth factor gene transfer restores cavernous angiogenesis and erectile function in a rat model of hypercholesterolemiaMolecular Therapy, Vol. 13, No. 4A Preservation Method Supporting Multipurpose Analysis of Long-stored SamplesCell Preservation Technology, Vol. 4, No. 1An optimized protocol for detection of E. coli β-galactosidase in lung tissue following gene transfer10 June 2005 | Histochemistry and Cell Biology, Vol. 124, No. 1Differential large-scale chromatin compaction and intranuclear positioning of transcribed versus non-transcribed transgene arrays containing β-globin regulatory sequencesJournal of Cell Science, Vol. 117, No. 19Changing intracellular compartmentalization of ?-galactosidase in the ROSA26 reporter mouse during embryonic development: A light- and electron-microscopic study1 January 2004 | The Anatomical Record, Vol. 279A, No. 2Gene Therapy of Erectile Dysfunction in the Rat with Penile Neuronal Nitric Oxide Synthase1Biology of Reproduction, Vol. 67, No. 1Treatment of Experimental (Trinitrobenzene Sulfonic Acid) Colitis by Intranasal Administration of Transforming Growth Factor (Tgf)-β1 Plasmid26 June 2000 | Journal of Experimental Medicine, Vol. 192, No. 1Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineageDevelopment, Vol. 126, No. 22Induction of Purkinje fiber differentiation by coronary arterialization9 November 1999 | Proceedings of the National Academy of Sciences, Vol. 96, No. 23 Vol. 27, No. 3 Follow us on social media for the latest updates Metrics Downloaded 564 times History Published online 22 August 2018 Published in print September 1999 Information© 2018 Author(s)PDF download