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Growth hormone cell phagocytosis in adenohypophysis of mosaic mice: morphological and immunocytochemical electron microscopy study.

An electron microscopy immunocytochemical study was performed to determine the expression pattern of growth hormone (GH) in mosaic mutant mice adenohypophysis. In normal condition GH was restricted to the secretory granules of all growth hormone cells. Mosaic mice adenohypophysis contained growth hormone cells which have distinctive GH labeled secretory granules at the level seen in control animals. Ultrastructurally, some GH cells of mosaic mice presented abnormalities, but labeling intensity of secretory granules in these cells was always comparable to the basal condition. The striking findings presence of two forms (simple and activated) of folliculo-stellate cells (FS) in close association trough gap or tight junction with GH cells localized especially near the perivascular space. Frequently, in cytoplasm of FS cells, large clusters containing fragments of GH labeled cell were present. Additionally, the existence of large intracellular, electron-lucent spaces, with remnant cellular material in parenchyma of mosaic mutant mice adenohypophysis could suggest intensive process of GH-cell destruction. Our electron microscopy immunocytochemical results provide evidence for loss of GH cells in mosaic mice by phagocytosis. We suppose that impaired body growth observed in mosaic mutant male rats may be, at least partially, a consequence of an alteration in somatotropic axis activity. Loss of GH cells in mosaic mice by phagocytosis supported by FS cells may contribute to this effect.

Animals↗

Fiber-mosaic adenovirus as a novel approach to design genetically modified adenoviral vectors.

Genetic modification of the adenovirus (Ad) capsid is one of the successful strategies to achieve viral retargeting. However, it has been widely recognized that structural constraints imposed by viral proteins limit the number and nature of incorporated targeting ligands and often hamper viral propagation. To address this issue, we propose a genetic fiber-mosaic virus (having two distinct fibers in one viral particle) as a means to facilitate fiber modifications. Fiber-mosaic virus having tandem fibers: a wild type (wt) fiber and second adjunctive fiber, will utilize natural viral entry for the conventional propagation of the vectors whereas, adjunctive fiber will serve multiple potential purposes such as targeting, purification, or imaging of viral particles via genetic incorporation of the corresponding functional moieties. We generated the mosaic adenovirus vector encoding two fibers: wild-type and adjunctive fiber--Fiber-Fibritin (FF) and confirmed incorporation of FF in the mosaic viral particles. We investigated binding specificity of the mosaic virus and the possible interference of the two fibers during virus life cycle. Fiber-mosaic Ad attained new binding properties provided by the second fiber, while preserving the binding ability attributed to the wt fiber. Our results suggest that the two fibers being presented and structurally separated on the viral particle may also function separately as binding counterparts for virus attachment. Therefore, the mosaic setting will allow more flexibility in Ad retargeting approaches.

Adenoviridae↗

Iso-orientation areas in the foveal cone mosaic.

The quality of the foveal cone mosaic in human and primate retinas is a basic parameter of spatial vision function. The present study uses digital-texture analysis procedures to analyze the crystalline order of inner segment sections containing the rod-free portions of foveal cone mosaics. Definition of the cone cross-sectional centers made possible by adequate preprocessing allows precise mapping of lattice vertices and differentiation of hexagonal positions by procedures for direct neighbor recognition. In a further step, the existence of subunits within the hexagonal areas is revealed by the determination of axial orientation. The lattice of the subunits is characterized by similar orientation and high positional correlation of its hexagonal units. The axial orientation of the areas differs from that of neighboring subunits by angular shifts of 10-15 deg and linear series of nonhexagonal irregularities demarcate the borders. Although larger patches with continuous hexagonal order occur in the surrounding rod-free regions, elevated degrees of disorder (30%) are found within the foveolar center (ca. 300 cones). Analysis of a mosaic showing labeled B cones (Szél et al., 1988) demonstrates that lattice disorder is in part associated with the blue cone subpopulation. The foveal mosaic from a glaucomatuous eye reveals severe lattice degradation throughout the rod-free zone, presumably due to extensive receptor loss. The low-frequency superstructure results in local sets of sampling grids (5'-8') with differing orientational bias. Besides a horizontal/vertical difference of mosaic compression (ca. 1:1.15), the present analysis gives no hints for the existence of systematic meridional anisotropies at the receptor mosaic level. The study reveals a discontinuous organization of the foveal mosaic and points to possible sources for the induction and location of lattice disorder.

Adolescent↗

A unique mosaic in the visual cortex of the reeler mutant mouse.

Numerous studies have revealed abnormal cytoarchitectonics in the reeler mouse brain. In the present study, acetylcholinesterase (AChE) histochemistry has revealed a distinctive mosaic within the occipital cortex of the reeler mouse. The mosaic does not appear until after the second postnatal week, perhaps in association with eye opening. AChE staining in the visual cortex of normal littermates does not exhibit a mosaic pattern, but rather, is present within bands or laminae. The AChE mosaic in reeler persists into adulthood. Immunocytochemical staining of the tenascin glycoprotein, an astrocyte-derived extracellular matrix molecule that is concentrated in boundaries around emerging functional patterns in the CNS, reveals a boundary-mosaic pattern in the first postnatal week. Dil axonal tracing in normal versus reeler mice indicates that the thalamocortical projections may also be associated with the AChE mosaic. The observation that a mosaic is unique to the occipital cortex of reeler mice suggests that it may evolve through abnormal cell and molecular interactions in the mutant cortex that normally lead to the development of functional visual representations.

Acetylcholinesterase↗

Effect of mosaicity in x-ray studies of critical behavior at the nematic to smectic-A transition.

Previous studies of critical behavior at the nematic to smectic-A transition by high-resolution x-ray scattering were performed using low magnetic fields of 0.1-0.8 T. In those studies, the transverse resolution was limited by the sample mosaicity which complicated data analysis. In order to understand the effect of sample mosaicity on the measured values of critical exponents, the divergence of the smectic order correlation lengths xi(||, perpendicular ) and susceptibility sigma(o) was studied in a magnetic field ranging from 0.25 to 5 T. The use of high (5 T) field reduced the sample mosaicity and improved the effective transverse resolution by almost two orders of magnitude. Three liquid crystals, two mixtures of 6th and 7th homologs of 4,4(')-dialkylazoxybenzene (DnAOB) and 4-n-octylcyanobiphenyl (8CB) were studied. 15 wt% (D6.15AOB) and 40 wt% (D6.4AOB) mixtures of D7AOB in D6AOB have a wide nematic range, while 8CB has a narrow nematic range. Analysis of the data at different fields revealed a different and proper way to apply the mosaicity correction. The Gaussian mosaicity correction was found to be temperature independent but significantly ( approximately 3.5 times) smaller than the width of the sharpest q( perpendicular )-scan, which has traditionally been used for mosaicity correction in all previous studies. The values of the critical exponents measured over almost four decades of reduced temperature were: nu(||)=0.79+/-0.02, nu( perpendicular )=0.69+/-0.02, gamma=1.46+/-0.04 for D6.15AOB; nu(||)=0.79+/-0.02, nu( perpendicular )=0.67+/-0.02, gamma=1.44+/-0.04 for D6.4AOB; and nu(||)=0.70+/-0.02, nu( perpendicular )=0.52+/-0.02, gamma=1.24+/-0.04 for 8CB. The results for the two mixtures suggest that in wide temperature range nematics, far from the tricritical point, the exponents may be material independent. No significant effects of mosaicity on the values of the coefficient c of the fourth-order term in the structure factor were observed.

Journal Article↗

The high-mosaicity illusion: revealing the true physical characteristics of macromolecular crystals.

Typical measurements of macromolecular crystal mosaicity are dominated by the characteristics of the X-ray beam and as a result the mosaicity value given during data processing can be an artifact of the instrumentation rather than the sample. For physical characterization of crystals, an experimental system and software have been developed to simultaneously measure the diffraction resolution and mosaic spread of macromolecular crystals. The contributions of the X-ray beam to the reflection angular widths were minimized by using a highly parallel, highly monochromatic synchrotron source. Hundreds of reflection profiles over a wide resolution range were rapidly measured using a charge-coupled device (CCD) area detector in combination with superfine phi-slicing data collection. The Lorentz effect and beam contributions were evaluated and deconvoluted from the recorded data. Data collection and processing is described. From 1 degrees of superfine phi-slice data collected on a crystal of manganese superoxide dismutase, the mosaicities of 260 reflections were measured. The average mosaicity was 0.0101 degrees (s.d. 0.0035 degrees ) measured as the full-width at half-maximum (FWHM) and ranged from 0.0011 to 0. 0188 degrees. Each reflection profile was individually fitted with two Gaussian profiles, with the first Gaussian contributing 55% (s.d. 9%) and the second contributing 35% (s.d. 9%) of the reflection. On average, the deconvoluted width of the first Gaussian was 0.0054 degrees (s.d. 0.0015 degrees ) and the second was 0.0061 degrees (s. d. 0.0023 degrees ). The mosaicity of the crystal was anisotropic, with FWHM values of 0.0068, 0.0140 and 0.0046 degrees along the a, b and c axes, respectively. The anisotropic mosaicity analysis indicates that the crystal is most perfect in the direction that corresponds to the favored growth direction of the crystal.

Crystallography, X-Ray↗

Automated microscopy system for mosaic acquisition and processing.

An automatic mosaic acquisition and processing system for a multiphoton microscope is described for imaging large expanses of biological specimens at or near the resolution limit of light microscopy. In a mosaic, a larger image is created from a series of smaller images individually acquired systematically across a specimen. Mosaics allow wide-field views of biological specimens to be acquired without sacrificing resolution, providing detailed views of biological specimens within context. The system is composed of a fast-scanning, multiphoton, confocal microscope fitted with a motorized, high-precision stage and custom-developed software programs for automatic image acquisition, image normalization, image alignment and stitching. Our current capabilities allow us to acquire data sets comprised of thousands to tens of thousands of individual images per mosaic. The large number of individual images involved in creating a single mosaic necessitated software development to automate both the mosaic acquisition and processing steps. In this report, we describe the methods and challenges involved in the routine creation of very large scale mosaics from brain tissue labelled with multiple fluorescent probes.

Journal Article↗

Cowpea Mosaic Virus-Encoded Protease Does Not Recognize Primary Translation Products of M RNAs from Other Comoviruses.

The protease encoded by the large (B) RNA segment of cowpea mosaic virus was tested for its ability to recognize the in vitro translation products of the small (M) RNA segment from the comoviruses squash mosaic virus, red clover mottle virus, and cowpea severe mosaic virus (CPsMV, strains Dg and Ark), and from the nepovirus tomato black ring virus. Like M RNA from cowpea mosaic virus, the M RNAs from squash mosaic virus, red clover mottle virus, CPsMV-Dg, and CPsMV-Ark were all translated into two large polypeptides with apparent molecular weights which were different for each virus and even for the two CPsMV strains. Neither the in vitro products from squash mosaic virus, red clover mottle virus, and CPsMV M RNAs nor the in vitro product from tomato black ring virus RNA-2 were processed by the cowpea mosaic virus-encoded protease, indicating that the activity of this enzyme is highly specific.

Journal Article↗

Characteristics of Streptomyces coelicolor A3(2) aerial spore rodlet mosaic.

Cytochemical analysis of Streptomyces coelicolor (A3(2) indicated that the aerial growth rodlet mosaic is a polysaccharide. Statistical analysis of frequency distributions of individual rodlet lengths from control and ether-reoriented spore mosaics indicated that the rodlet fibrillar image is the result of individual particulates, rather than evaginations in a continuous sheet of material. A model of the mature sport envelope was developed from freeze-etch-replicated, thin-sectioned, and critical point dried S. coelicolor A3(2) mature spores. The rodlet mosaic was situated between the outer spore wall and an external granuloma matrix. Mixture spore envelope layers from the inner surface to the external surface are plasma membrane, inner spore wall, outer spore wall, rodlet mosaic, an undefined granular matrix, and the sheath. The granular matrix had an uneven thickness and much of the matrix was frequently absent from the interspore spaces of mature spore chains. Streptomyces coelicolor A3(2) mosaic rodlets were isolated by acetic acid refluxing, then ethanol precipitation. Complete acid hydrolysis of rodlets released on sugar which cochromatographed with D-glucosamine-HCl and released acetic acid at 139% of the expected level. Cell associated rodlet mosaics and isolated mosaic rodlets were hydrolyzed with chitinase. Infrared spectra of isolated rodlets were similar to crab chitin spectra.

Acetates↗

MOSAIC: Multimodal Stroke Assessment Using Computed Tomography: novel diagnostic approach for the prediction of infarction size and clinical outcome.

BACKGROUND AND PURPOSE: With new CT technologies, including CT angiography (CTA), perfusion CT (PCT), and multidetector row technique, this method has regained interest for use in acute stroke assessment. We have developed a score system based on Multimodal Stroke Assessment Using CT (MOSAIC), which was evaluated in this prospective study. METHODS: Forty-four acute stroke patients (mean age, 63.8 years) were enrolled within a mean of 3.0+/-1.9 hours after symptom onset. The MOSAIC score (0 to 8 points) was generated by results of the 3 sequential CT investigations: (1) presence and amount of early signs of infarction on noncontrast CT (NCCT; 0 to 2 points), (2) stenosis (>50%) or occlusion of the distal internal carotid or middle cerebral artery on CTA (0 to 2 points), and (3) presence and amount of reduced cerebral blood flow on 2 adjacent PCT slices (0 to 4 points). The predictive value of the MOSAIC score was compared with each single CT component with respect to the final size of infarction and the clinical outcome 3 months after stroke by use of the modified Rankin Scale (mRS) and the Barthel Index (BI). RESULTS: Among the CT components, PCT showed the best correlation to infarction size (r=0.75) and clinical outcome (r=0.60 to 0.62) compared with NCCT (r=0.43 to 0.58) and CTA (r=0.47 to 0.71). The MOSAIC score showed consistently higher correlation factors (r=0.67 to 0.78) and higher predictive values (0.73 to 1.0) than all single CT components with respect to outcome measures. A MOSAIC score <4 predicted independence with 89% to 96% likelihood (mRS </=2, BI >/=90); a MOSAIC score <5 predicted fair outcome with 96% to 100% likelihood (mRS </=3, BI >/=60). CONCLUSIONS: The MOSAIC score based on multidetector row CT technology is superior to NCCT, CTA, and PCT in predicting infarction size and clinical outcome in hyperacute stroke.

Acute Disease↗

Standard microlithographic mosaics to assess endothelial cell counting methods by light microscopy in eye banks using organ culture.

PURPOSE: To develop standard microscopic hexagonal mosaics mimicking the human corneal endothelium for quality control of endothelial cell density (ECD) measurement and verification of cell counting strategy by light microscopy in eye banks using organ culture. METHODS: A standard slide, the Keratotest, was developed with 10 laser-engraved mosaics and different predetermined "cell" densities representing the range of ECDs observed routinely. Horizontal and vertical micrometric scales were etched adjacently to each mosaic, and a standard microscopy resolution test pattern was included. The Keratotest was applied to assess the reliability of a computer-assisted analyzer developed for corneal endothelial evaluation based on light microscopy images. RESULTS: The Keratotest consisted of 10 microlithographic homogeneous mosaics of 1-mm2 printed area and 1.2-microm cell boundary thickness. The micrometric scale associated with each mosaic aided in simultaneous verification of microscope calibration, and the test pattern aided in checking the microscope resolution. The design was unalterable and reproducible, and the glass slide incorporated in a carbon fiber support ensured easy handling and safe transport. Evaluation of the Keratotest mosaics by the computer-assisted analyzer found a high level of agreement (error margin between +0.12 and -0.46%) with the laser-engraved cell density. CONCLUSIONS: This prototype device enabled assessment of reliability of ECD measurement in eye banks. It also allowed verification of the calibration and resolution of light microscopes. Periodic validation of counting procedure in eye banks with mosaics of known "cell" densities should be useful for standardization of donor corneal tissue quality control.

Cell Count↗

The effective orifice area/patient aortic annulus area ratio: a better way to compare different bioprostheses? A prospective randomized comparison of the Mosaic and Perimount bioprostheses in the aortic position.

BACKGROUND AND AIM OF THE STUDY: The aim of this prospective, randomized study was to compare the hemodynamic performance of the Medtronic Mosaic and Edwards Perimount bioprostheses in the aortic position, and to evaluate prosthesis-specific differences in valve sizing and valve-size labeling. METHODS: Between August 2000 and September 2002, 139 patients underwent isolated aortic valve replacement (AVR) with the Mosaic (n = 67) or Perimount (n = 72) bioprosthesis. Intraoperatively, the internal aortic annulus diameter was measured by insertion of a gauge (Hegar dilator), while prosthesis size was determined by using the original sizers. Transthoracic echocardiography was performed to determine hemodynamic and dimensional data. As the aim of AVR is to achieve a maximal effective orifice area (EOA) within a given aortic annulus, the ratio of EOA to patient aortic annulus area was calculated, the latter being based on annulus diameter measured intraoperatively. RESULTS: Operative mortality was 2.2% (Mosaic 3.0%; Perimount 1.4%; p = NS). Upsizing (using a prosthesis larger in labeled valve size than the patient's measured internal aortic annulus diameter) was possible in 28.4% of Mosaic patients and 8.3% of Perimount patients. The postoperative mean systolic pressure gradient ranged from 10.5 to 22.2 mmHg in the Mosaic group, and from 9.4 to 12.6 mmHg in the Perimount group; it was significantly lower for 21 and 23 Perimount valves than for 21 and 23 Mosaic valves. The EOA ranged from 0.78 to 2.37 cm2 in Mosaic patients, and from 0.95 to 2.12 cm2 in Perimount patients. When indexing EOA by calculating the ratio of EOA to patient aortic annulus area to adjust for variables such as patient anatomy and valve dimensions, there was no significant difference between the two bioprostheses. CONCLUSION: Comparisons of absolute EOA values grouped by the manufacturers' valve sizes are misleading because of specific differences in geometric dimensions. The EOA:patient aortic annulus area ratio provides a new hemodynamic index which may facilitate objective comparisons between different valve types.

Aged↗

Evaluation of the incidence and significance of the "mosaic pattern" in patients with cirrhosis, noncirrhotic portal fibrosis, and extrahepatic obstruction.

Mosaic pattern of gastric mucosa has been reported to be a sensitive and specific criterion for the diagnosis of portal hypertension and an important marker of nonvariceal upper gastrointestinal bleeding. So that the validity of this endoscopic sign could be assessed, 136 patients with portal hypertension, 25 chronic alcoholics without portal hypertension, and 366 controls were carefully endoscoped. Mosaic pattern was significantly (p less than 0.01) more common in portal hypertension patients (7.4%) than in controls (1.4%). It was not seen in chronic alcoholics. The incidence of mosaic pattern was 10.9% in cirrhotics, 2.9% in noncirrhotic portal fibrosis, and 5.4% in extrahepatic portal obstruction patients; the differences were not significant. Mosaic pattern was significantly (p less than 0.01) more often seen in postsclerotherapy (13.8%) than in presclerotherapy patients (2.6%). Bleeding from nonvariceal causes was uncommon, and was seen in only one patient (0.8%) showing mosaic pattern. Endoscopic gastric biopsies from areas showing mosaic pattern did not reveal any vascular abnormalities. In conclusion, gastric mucosal lesions are not very common in Indian patients with portal hypertension. In our experience, "mosaic pattern" is not a useful diagnostic feature in portal hypertension patients.

Adolescent↗

Rare trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: karyotype/phenotype correlations.

In order to determine the significance of trisomy mosaicism of an autosome other than chromosomes 13, 18, 20, and 21, 151 such cases diagnosed prenatally through amniocentesis were reviewed. These rare trisomy mosaicism cases include 54 from 17 cytogenetic laboratories, 34 from a previous North American mosaicism survey, and 63 from published reports. All were cases of true mosaicism with information available on pregnancy outcome, and with no evidence of biased ascertainment. There were 11 cases of 46/47, +2; 2 of 46/47, +3; 2 of 46/47, +4; 5 of 46/47, +5; 3 of 46/47, +6; 8 of 46/47, +7; 14 of 46/47, +8; 25 of 46/47, +9; 2 of 46/47, +11; 23 of 46/47, +12; 5 of 46/47, +14; 11 of 46/47, +15; 21 of 46/47, +16; 7 of 46/47, +17; 1 of 46/47, +19; and 11 of 46/47, +22. As to the risk of an abnormal outcome, the data showed a very high risk (> 60 per cent) for 46/47, +2, 46/47, +16, and 46/47, +22; a high risk (40-59 per cent) for 46/47, +5, 46/47, +9, 46/47, +14, and 46/47, +15; a moderately high risk (20-39 per cent) for 46/47, +12; a moderate risk (up to 19 per cent) for 46/47, +7 and 46/47, +7 and 46/47, +8; a low risk for 46/47, +17; and an undetermined risk, due to lack of cases, for the remaining autosomal trisomy mosaics. Most cases were evaluated at birth or at termination, so subtle abnormalities may have escaped detection and developmental retardation was not evaluated at all. Comparison of the phenotypes of prenatally diagnosed abnormal cases and postnatally diagnosed cases with the same diagnosis showed considerable concordance. Since the majority of anomalies noted are prenatally detectable with ultrasound, an ultrasound examination should be performed in all prenatally diagnosed cases. In cytogenetic confirmation studies, the data showed much higher confirmation rates in cases with abnormal outcomes than in cases with normal outcomes [81 per cent vs. 55 per cent for fibroblasts (from skin, fetal tissue, and/or cord); 88 per cent vs. 46 per cent for placental cells; 22 per cent vs. 10 per cent for blood cells]. The confirmation rate reached 85 per cent when both fibroblasts and placental tissues were studied in the same case (with trisomic cells found in one or the other, or both). Therefore, one must emphasize that both fibroblasts and placental tissues should be studied. Except for 46/47, +8 and 46/47, +9, PUBS is of limited value for prenatal diagnosis of rate trisomy mosaicism. DNA studies for UPD are suggested for certain chromosomes with established imprinting effects, such as chromosomes 7, 11, 14, and 15, and perhaps for chromosomes 2 and 16, where imprinting effects are likely.

Adolescent↗

Mosaic inv dup(8p) marker chromosome with stable neocentromere suggests neocentromerization is a post-zygotic event.

Marker chromosomes containing active human neocentromeres have been described in individuals where the chromosomes are non-mosaic, suggesting that they are mitotically stable, but also in individuals where there is mosaicism, raising the possibility of neocentromere instability. We report two independently ascertained individuals who are mosaic for a supernumerary marker chromosome, shown by reverse chromosome painting to have an 8p origin, resulting in mosaicism for tetrasomy 8p23.1-->pter in the patient. The markers have a primary constriction but show no detectable centromeric alpha-satellite DNA. The marker in Patient 1 demonstrated no centromere protein CENP-B binding, but associated with nine different functionally critical centromere proteins. Investigation of peripheral blood lymphocytes from this patient on five separate occasions over a 13-year period showed 23-46% mosaicism for the marker chromosome with no decrease in incidence. In vitro investigation of primary and secondary sub-clones of a lymphoblast cell line derived from the patient demonstrated 100% stability of the marker chromosome indicating that neocentromere instability is unlikely to be responsible for the mosaicism in the patient. This and other available data support a general model of neocentromerization as a post-zygotic event, irrespective of whether the supernumerary chromosome fragment has arisen during meiosis or post-fertilization at mitosis.

Adolescent↗

Assessment of the proportion of transgene-bearing sperm by fluorescence in situ hybridization: a novel approach for the detection of germline mosaicism in transgenic male founders.

Genetic mosaicism is frequent among transgenic animals produced by pronuclear microinjection. A successful method for the screening of founder animals for germline mosaicism prior to mating would greatly reduce the costs associated with the propagation of the transgenic lines, and improve the efficiency of transgenic livestock production. With this aim, we have devised a simple method to detect integrated transgenes in individual spermatozoa using fluorescence in situ hybridization (FISH). The experiments reported here were undertaken to investigate the efficiency of this FISH-based approach to accurately evaluate the proportion of transgene-bearing sperm and to be applied for the detection of potential germline mosaics. Sperm samples from mice homozygous and hemizygous for a beta-lactoglobulin transgene were analyzed in a first set of experiments. A high hybridization efficiency was achieved, and the proportions of transgene-positive sperm cells in both homozygous (94.8-98.2%) and hemizygous (49.8-51.9%) animals were close to the expected frequencies (100 and 50%, respectively). To evaluate the sensitivity of the assay more directly, simulated mosaic samples with 5, 10, 15, 20 and 40% of transgene-bearing spermatozoa were then prepared and analyzed by FISH. Significant differences in the frequency of transgene-positive sperm were observed between all mosaic samples, indicating that even small deviations (5%) from the expected 50% transgene transmission rate in a founder animal could be reliably detected with our assay. Therefore, the method proposed represents a novel approach for the identification of germline mosaic founder males in livestock transgenic projects and a much more economic and faster alternative to breeding.

Animals↗

Variable clinical expression of mosaic trisomy 16 in the newborn infant.

Trisomy 16 is common in embryos and fetuses aborted early during development. Mosaicism for trisomy 16 is sometimes encountered during prenatal diagnosis, particularly with chorionic villi biopsy specimens, and, until recently, was thought to be confined to the placenta. However, recently, several liveborn infants with trisomy 16 mosaicism have been described. We report on an additional liveborn infant with trisomy 16 mosaicism and compare the clinical findings with those of the previously reported cases in an attempt to delineate a mosaic trisomy 16 syndrome. Cytogenetic analysis from our patient showed that there was a different proportion of abnormal cells in different tissues and that the anomaly was undetectable in blood lymphocyte cultures. This observation was consistent with some of the previous reports. DNA analysis of parents and child was carried out using a polymorphic dinucleotide marker that maps to the long arm of chromosome 16. This analysis showed that the extra chromosome 16 in the infant was maternal in origin and suggested that the nondisjunction was probably a first meiotic division error. Our results suggest that an investigation of multiple tissues is required before concluding that mosaicism is confined to the placenta. We conclude that a finding of trisomy 16 mosaicism at prenatal diagnosis should be regarded with extreme caution. This diagnosis may be associated with a highly variable phenotype that may occasionally be compatible with extrauterine life.

Abnormalities, Multiple↗

Prenatal diagnosis of chromosome 4 mosaicism: prognostic role of cytogenetic, molecular, and ultrasound/MRI characterization.

Trisomy 4 mosaicism is extremely rare: herein we report the cytogenetic and molecular characterization and prenatal US findings of a case diagnosed prenatally. The diagnosis of level III mosaicism was established in cultured amniotic fluid cells (22.5%). At 22 weeks gestation, micrognathia and hypotelorism were suspected at 2-D sonography, and confirmed at 3-D examination. In addition, 2-D US showed cerebellar hypoplasia associated with borderline ventriculomegaly (confirmed at magnetic resonance imaging, MRI), spine deformity (hemivertebra), and a complete atrioventricular septal defect (AVSD). The pregnancy was terminated. Trisomy 4 mosaicism was confirmed in placental and fetal skin cultured cells. The cord blood karyotype was normal. Molecular analysis excluded uniparental disomy of chromosome 4, and indicated that the trisomy 4 was of maternal meiotic origin. In presence of chromosome 4 mosaicism, accurate fetal sonography and echocardiography are mandatory. Low level mosaicism and normal echographic examinations seem to be associated with good prognosis. In postnatal life, chromosome 4 mosaicism should be suspected, and cytogenetic analysis proposed of further tissues (i.e., skin), in presence of craniofacial dysmorphism, cardiac defects, and abnormal hands/feet, even if mental development is appropriate or only slightly impaired.

Abnormalities, Multiple↗