Shape variation in cranium, mandible and teeth in selected mouse strains.

There are different strains of laboratory mouse used in many different fields. These strains differ anatomically. In order to determine these anatomical differences, shape analysis was conducted according to species. CD-1, C57bl/6 and Balb-c strains were preferred to study these differences. Forty-eight adult mouse strains belonging to these strains were utilized. The bones were photographed and geometric morphometry was applied to these photographs. Principal Component Analysis was applied to determine shape variations. In Principal component 1 for cranium, CD-1 and C57bl/6 strain groups showed different shape variations, while Balb-c strain group showed similar shape variations to the other strain groups. Principal Component 1 for the mandible separated the CD-1 and C57bl/6 strain groups in terms of shape variation. Principal Component 2 explained most of the variation between the C57bl/6 and CD-1 lineage groups. In PC1 for molars, the CD-1 group showed a different shape variation from the other groups. Mahalanobis distances and Procrustes distances were measured using Canonical variance analysis to explain the differences between the lineage groups. These measurements were statistically significant. For cranium, in canonical variate 1, CD-1 group of mouse and Balb-c group of mouse were separated from each other. In canonical variate 2, C57bl/6 group of mouse were separated from the other groups. For mandible, Balb-c group of mouse in canonical variate 1 and CD-1 group of mouse in canonical variate 2 were separated from the other groups. For molars, CD-1 group of mouse in canonical variate 1 and Balb-c group of mouse in canonical variate 2 were separated from the other groups. It was thought that these anatomical differences could be caused by genotypic factors as well as dietary differences and many different habits that would affect the way their muscles work.

Gross anatomy of vascular supply and drainage of mammary fat pads in mice models.

This work extensively studied the vasculature of mice mammary fat pads (BALB/c and C57BL/6) with special reference to haematogenous drainage routes. Mammary fat pads were five pairs (first cervical, second and third thoracic, fourth abdominal and fifth inguinal), bilaterally symmetrical, extending laterally and continuously with the subcutaneous fascia. The superficial cervical artery and vein primarily accomplished the blood vasculature of the first mammary fat pad, while the lateral thoracic and external thoracic arteries and veins supplied the second and third mammary fat pads. The superficial cervical vein (found parallel to the superficial cervical artery) drained into the external jugular vein. The lateral thoracic artery and external thoracic artery branched almost at the same level as the axillary artery (branch of subclavian artery), the latter being more medial in position. However, in some specimens, the branching of both arteries appeared to be at the same level, and their origins were indistinguishable. The lateral thoracic vein that was parallel to the lateral thoracic artery drained to the axillary vein close to the drainage of the external thoracic vein. The lateral thoracic, superficial caudal epigastric, iliolumbar and external thoracic arteries and veins vascularized the fourth mammary fat pad and displayed anastomosis among themselves. The iliolumbar vein (found parallel to the iliolumbar artery) drained into the inferior vena cava. The superficial caudal epigastric vein (found parallel to the superficial caudal epigastric artery (SCaEA)) drained into the femoral vein. Unlike humans, the internal thoracic artery and vein did not participate in the vasculature of mammary fat pads. The SCaEA and vein supplied blood and drained the fifth mammary fat pad. The anatomical continuity of the fourth and fifth mammary fat pads provided common drainage for both mammary fat pads. The BALB/c and C57BL/6 mice strains studied did not differ in topography and size of mammary fat pads. The vascular supply and drainage of the mammary fat pads also did not differ in the strains studied. Only minor variations could be noted in the small veins draining into the lateral thoracic vein. Lateral tributaries seen in the terminal end of the lateral thoracic vein were absent in the C57BL/6 mice.

Evaluating the Reproducibility of Mouse Anatomy under Rotation in a Custom Immobilization Device for Conformal FLASH Radiotherapy.

The observation of an enhanced therapeutic index for FLASH radiotherapy in mice has created interest in practical laboratory-based FLASH irradiators. To date, systems capable of 3D conformal FLASH irradiation in mice have been lacking. We are developing such a system, incorporating a high-current linear accelerator to produce a collimated X-ray beam in a stationary beamline design, rotating the mouse about a longitudinal axis to achieve conformal irradiation from multiple beam directions. The purpose of this work was to evaluate the reproducibility of mouse anatomy under rotation at speeds compatible with conformal FLASH delivery. Three short-hair mice and two hairless mice were immobilized under anesthesia in body weight-specific contoured plastic molds, and subjected to three rotational (up to 3 revolutions/s) and two non-rotational movement interventions. MicroCT images were acquired before and after each intervention. The displacements of 11 anatomic landmarks were measured on the image pairs. The displacement of the anatomical landmarks with any of the interventions was 0.5 mm or less for 92.4% of measurements, with a single measurement out of 275 (11 landmarks × 5 interventions × 5 mice) reaching 1 mm. There was no significant difference in the displacements associated with rotation compared to those associated with moving the immobilized mouse in and out of a scanner or with leaving the mouse in place for 5 min with no motion. There were no significant differences in displacements between mice with or without hair, although the analysis is limited by small numbers, or between different anatomic landmarks. These results show that anatomic reproducibility under rotation speed corresponding to FLASH irradiation times appears to be compatible with conformal/stereotactic irradiation in mice.

Características morfocuantitativas de la glándula submandibular de ratón (Mus musculus) / Morphocuantitative characteristics of the mouse (Mus musculus) submandibular gland

El ratón (Mus musculus) es un buen modelo animal de experimentación, donde sus glándulas salivales han sido utilizadas en estudios, especialmente de tipo preclínico. Sin embargo, las diferencias en la morfología de estas glándulas y, en particular de las submandibulares, entre humanos y roedores no son de conocimiento común. Por lo anterior, el objetivo de este estudio fue conocer las características morfocuantitativos de la glándula submandibular del ratón macho C57BL/6. Se utilizaron cinco ratones macho, cepa C57BL/ 6, de 11 a 13 semanas de nacidos, con un peso promedio de 30 g. Luego de su ambientación, los ratones fueron eutanasiados. Para el análisis histológico, las glándulas fueron extraídas y fijadas en formalina tamponada por 48 horas, procesada para su inclusión en paraplast y teñidas con hematoxilina y eosina, azul alcián pH 2,5, ácido peryódico de Schiff y Picrosirius Red. Se determinaron las características estereológicas de densidad de longitud (LVcond), de volumen (VVcond) y de superficie (SVcond) de los conductos. En las células acinares se evaluó la densidad de número (NVcel) y la densidad de volumen (VVcel). Para cada variable se obtuvo la media ± desviación estándar. La glándula submandibular se encontraba organizada de manera lobulada, cuyo parénquima era de tipo túbuloacinar mixto con predominio seroso, que se conectaba a través de conductos. Las células acinares presentaban reacción positiva para azul alcián y ácido peryódico de Schiff. El estroma de la glándula contenía principalmente colágeno tipo 1. Los resultados de las mediciones estereológicas fueron: LVcond = 220,02 ± 50,51 mm/mm3; VVcond = 50,48 ± 9,55 %; SVcond = 26,39 ± 5,45 mm2/mm3; NVcel = 16,85 x 104 ± 9,13 × 104/mm3; VVcel = 24,98 ± 6,22 %. Con los análisis presentados es posible realizar investigaciones experimentales, considerando las similitudes y diferencias morfocuantitativas que presenta la glándula submandibular de ratón macho, cepa C57BL/6 con la del humano.

The mouse (Mus musculus) is a good experimental animal model, where murine salivary glands have been widely used in research by their similarities with human glands. Stereology is a tool that has to demonstrated to be valuable in biomedical researc h. Therefore, the objective was to realize an analogy between morphology, function and morpho-quantitative characteristics of the C57BL/6 mouse submandibular gland. Five male mice, C57BL/6, from 11 to 13 weeks old were used, with an average weight of 30 g. After seven days, the mice were euthanized and the samples were extracted. Then, these were processed following the conventional histological processing protocol and stained with H&E, Picrosirius Red, AA and PAS. Finally, the histological and stereological analysis of the samples was performed. In the glandular ducts the length density (LVcond), volume density (VVcond) and surface density (SVcond) were determined; whereas, in the acinar cells the density of number (NVcel) and the density of volume (VVcel) were evaluated. For each stereological variable the mean ± standard deviation was obtained. The histological study revealed no discrepancies as previously described. Descriptive statistical analysis revealed the following: LVcond = 220.02 ± 50.51 mm/mm3; VVcond = 50.48 ± 9.55 %; SVcond = 26.39 ± 5.45 mm2/mm3; NVcel = 168467.38 ± 91288.67 /mm3 and VVcel = 24.98 ± 6.22 %. From this study, it will be possible to conduct comparative experimental research analyzing quantitative results from those presented in this research. From this study, it will be possible to carry out comparative experimental research, analyzing quantitative results from those presented in this investigation.

Commonly used mouse strains have distinct vascular properties.

Mice are the most common animal model to investigate human disease and explore physiology. Mice are practical, cost efficient, and easily used for genetic manipulations. Although variability in cardiac structure and function among mouse strains is well noted, the effect of mouse strain on vascular stiffness indices is not known. Here, we compared mouse strain-dependent differences in key vascular stiffness indices among frequently used inbred mouse strains-C57Bl/6J, 129S, and Bl6/129S. In young healthy animals, baseline blood pressure and heart rate were identical in all strains, and independent of gender. However, both active in vivo and passive ex vivo vascular stiffness indices exhibited distinct differences. Specifically, both male and female 129S animals demonstrated the highest tensile stiffness, were least responsive to acetylcholine-induced vasorelaxation, and showed the lowest pulse wave velocity (PWV), an index of in vivo stiffness. C57Bl/6J mice demonstrated the highest PWV, lowest tensile stiffness, and the highest response to acetylcholine-induced vasorelaxation. Interestingly, within each strain, female mice had more compliant aortas. C57Bl/6J mice had thinner vessel walls with fewer layers, whereas 129S mice had the thickest walls with the most layers. Values in the Bl6/129S mixed background mice fell between C57Bl/6J and 129S mice. In conclusion, we show that underlying vascular properties of different inbred wild-type mouse strains are distinct, despite superficial similarities in blood pressure. For each genetic modification, care should be taken to identify proper controls, and conclusions might need to be verified in more than one strain to minimize the risk of false positive studies.

Developmental milestones in neonatal and juvenile C57Bl/6 mouse - Indications for the design of juvenile toxicity studies.

There is a growing demand for wild type mice and mouse models of disease that may be more representative of human conditions but there is little information on neonatal and juvenile mouse anatomy. This project produces sound and comprehensive histology background data on the developing neonatal mouse at different time points from Day 0 until Day 28. The work describes optimal methods for tissue harvesting, fixation and processing from the neonatal and juvenile mice which can be used in routine toxicology studies. A review of the available literature revealed inconsistencies in the developmental milestones reported in the mouse. Although it is true that the sequence of events during the development is virtually the same in mice and rats, important developmental milestones in the mouse often happen earlier than in the rat, and these species should not be used interchangeably.

Applicability of vital staining and tissue clearing to vascular anatomy and melanocytes' evaluation of temporal bone in six laboratory species.

The purpose of the present study was to define the applicability of tissue clearing to the field of otology. We combined tissue clearing with vital staining perfusion via a pumping system to examine the vascular anatomy of temporal bones in laboratory animals. We used six different types of species including Korean wild mouse, mouse, Mongolian gerbil, hamsters and Guinea pigs. A mixture of Alcian blue reagent and 4% paraformaldehyde was circulated throughout the entire circulatory system of the animal via a perfusion pump system. Transparency images were obtained from the temporal bones according to the protocol of the SunHyun 3D Imaging Kit. In examining the inner surface of the tympanic membrane, flaccid part (pars flaccida) was positioned along the entire marginal area in Guinea pig. In the Guinea pig, unlike the other species, the cortical bone of the mastoid (bullae) was easily removed using cold instruments, allowing a direct approach to the enclosed structures. The distribution and pattern of cochlea melanocytes were compared among the species. "Mobius strip"-like accumulated melanocytes in vestibules were shown in both the Korean wild mouse and mouse. The collateral blood supply to the cochlea in six different species was checked in various pattern. Combining dye infusion with tissue-clearing techniques, we documented the middle ear and transparent inner ear structures in six different species. The information and associated images will help other researchers to develop hypotheses and design experimental investigations.

Validation of Sysmex XT-2000iV analyzer-generated quantitative bone marrow differential counts in cynomolgus monkeys, Beagle dogs, and CD-1 mice.

BACKGROUND: In a previous study, the validation of rat bone marrow (BM) collection, processing, and analysis using the Sysmex XT-2000iV (Sysmex Corporation, Kobe, Japan) hematology analyzer showed that the Sysmex hematology analyzer produced BM differential counts that were comparable to those obtained with microscopic differential counts. OBJECTIVE: This study was conducted to expand the validation of the Sysmex TNCC (total nucleated cell count) and 5-part BM differential in cynomolgus monkeys, Beagle dogs, and CD-1 mice, which are alternate species that are also frequently used in preclinical safety studies. METHODS: The Sysmex 5-part BM differential counts were generated with a two-step process, whereby proliferating and maturing erythroid and myeloid cells were determined by preset gating and lymphocytes were determined using species-specific B- and T-lymphocyte antibodies and a magnetic cell-sorting method (MACS). Agreement with microscopic myelograms with 500-cell differential counts was determined from BM suspensions of 62 cynomolgus monkeys, 47 Beagle dogs, and 44 CD-1 mice. RESULTS: The correlation coefficients between methods for myeloid to erythroid (M:E) ratios in all three species was > 0.928. The Bland-Altman differences between methods were approximately ± 0.3 units for the M:E ratio in dogs and mice, and +0.6 and -0.4 in monkeys. The upper limits of agreement for all three species were ≤7% for maturing myeloid cells, ≤6% for maturing erythroid cells, and ≤4% for proliferating myeloid cells, proliferating erythroid cells, and lymphocytes. CONCLUSIONS: The Sysmex XT-2000iV produces an automated M:E ratio and a 5-part differential count equivalent to microscopic differential counts in cynomolgus monkeys, Beagle dogs, and CD-1 mice.

Impact of bedding volume on physiological and behavioural parameters in laboratory mice.

The standard housing temperature in animal facilities is substantially below the lower critical temperature of mice. This does not only endanger animal welfare, it can also jeopardize scientific research as cold stress has a major impact on mouse physiology. There is some evidence that deep bedding, comparable to nesting material, can help mice to reduce heat loss. Whenever changes are applied to the cage environment, the potential impact on experimental results, including variation, needs to be assessed. An increased variation can result in a conflict between reduction and refinement, when more animals are needed for significance due to the housing design. The aim of this study was to assess the impact of different bedding volumes (0.5 L, 1.5 L and 6 L per type III cage) on mean values and coefficient of variation (CV) of physiological (pentobarbital sleeping time, blood and anatomical parameters) and behavioural parameters (open-field and novel object recognition tests) of group-housed female and male BALB/c and C57BL/6 mice. A larger bedding volume did not interfere with the CVs, but influenced mean values of organ weights and tail lengths. Mice housed on deeper bedding showed a significant reduction in adrenal, liver, kidney and heart weights as well as an increase in tail lengths; these anatomical changes are akin to warm adaptation, and were previously observed for mice housed under warmer environments. A larger bedding volume appears to be a sensible way to reduce cold stress for laboratory mice without increasing variation in experimental results.

Mice with infectious colitis exhibit linear growth failure and subsequent catch-up growth related to systemic inflammation and IGF-1.

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C rodentium-infected, partially-attenuated C rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the wild-type C rodentium group). Relative to the uninfected group, mice infected with wild-type C rodentium exhibited temporal associations of lower food intake, weight loss, linear-growth failure, higher IL-6 and TNF-α and lower IGF-1. However, relative to the pair-fed group, the C rodentium-infected group only differed significantly by linear growth and systemic inflammatory cytokines. Between post-infection days 15-20, the infected group exhibited resolution of systemic inflammation. Between days 16-20, both wild-type C rodentium and pair-fed groups exhibited rapid linear-growth velocities exceeding the uninfected and mutant C rodentium groups; during this time levels of IGF-1 increased to match the uninfected group. We submit this as a model providing important opportunities to study mechanisms of catch-up growth related to intestinal inflammation. We conclude that in addition to known effects of weight loss, infection with C rodentium induces linear-growth failure potentially related to systemic inflammation and low levels of IGF-1, with catch-up of linear growth following resolution of inflammation.

In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain.

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 µm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.

Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex.

Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and postmigratory expression of these CPN-enriched genes in deep layers are highly conserved (e.g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g., EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships.

A comparison of sexing methods in fetal mice.

Accurate mouse sexing is vital when conducting research examining sexual dimorphisms. Late fetal and newborn mouse pups are more immature than many previously described sexing methods allow. This study compares the sexing accuracy of a newly described internal gonad sexing method to a recently described peritoneal pigmentation sexing method in embryonic day 20 C57BL/6J mouse pups, using Sry genotyping to confirm the sex. The internal gonad sexing method was found to be highly accurate, while the peritoneal pigmentation method was slightly less accurate. Therefore, while Sry genotyping remains the gold standard, immediate and less expensive sexing methods can be performed accurately as early as the late fetal period in C57BL/6J mice.

Unusual anatomical origins of the coronary arteries in C57BL/6 mice. Are they strain-specific?

A previous manuscript [Fernández B, et al. (2008) J Anat 212, 12] reported on the unusual coronary artery patterns in mice belonging to the C57BL/6 strain. The aim here was to elucidate whether this pattern is unique to C57BL/6 mice or appears in other laboratory mouse strains and in wild-living mice. Stereomicroscopy, scanning electron microscopy, light microscopy and a corrosion cast technique were used to examine 597 adult mice belonging to three inbred strains (C57BL/6, Balb/c, DBA/2), three outbred stocks (CD1, OF1, NMRI) two hybrid lines (129sv × BL/6, CD2F1) and wild mice. It was shown that lock-like ostium is an exclusive trait of C57BL/6 mice, whereas left septal artery, accessory ostium, high take-off, intramural course and solitary ostium in aorta are all present in the different laboratory strains and wild mice included in the present study. However, each mouse population shows a specific incidence of these coronary conditions. Several clinically relevant human coronary artery anomalies are present in healthy mice from different strains that may serve as animal models for humans. These results should be taken into consideration in research concerning the murine coronary system, especially in coronary artery occlusion experiments and in studies on cardiovascular developmental biology using murine mutant lines.

Postnatal Development of the Craniofacial Skeleton in Male C57BL/6J Mice.

C57BL/6J is one of the most commonly used inbred mouse strains in biomedical research, including studies of craniofacial development and teratogenic studies of craniofacial malformation. The current study quantitatively assessed the development of the skull in male C57BL/6J mice by using high-resolution 3D imaging of 55 landmarks from 48 male mice over 10 developmental time points from postnatal day 0 to 90. The growth of the skull plateaued at approximately postnatal day 60, and the shape of the skull did not change markedly thereafter. The amount of asymmetry in the craniofacial skeleton seemed to peak at birth, but considerable variation persisted in all age groups. For C57BL/6J male mice, postnatal day 60 is the earliest time point at which the skull achieves its adult shape and proportions. In addition, C57BL/6J male mice appear to have an inherent susceptibility to craniofacial malformation.

Long-Term Provision of Environmental Resources Alters Behavior but not Physiology or Neuroanatomy of Male and Female BALB/c and C57BL/6 Mice.

Few studies have evaluated the long-term effects of providing environmental resources to mice. This consideration is important given that mice are often maintained in vivaria for months. We evaluated the effects of providing simple cage resources (wood wool, cotton nesting material, a plastic tunnel, and oat cereal) compared with standard housing (solid-bottom cage with hardwood chips) to group-housed adult male and female C57BL/6 and BALB/c mice (n = 20/sex/strain/group) over 6 mo to determine whether these resources had a lasting effect on animal physiology, anatomy, and behavior. Body weights increased in all groups over time but were proportionately higher in male and female BALB/c mice housed in resource-supplemented environments. Throughout the study, adding environmental resources had no effect on hematology and lymphocyte subsets, fecal corticoid metabolite levels, response to LPS injection, or dendritic spine length or density. Strain- or sex×environmentspecific changes occurred in dark-light activity and thermal nociceptive responses. Dominant agonistic behaviors, abnormal conspecific sexual behaviors, and social nonagonistic behaviors demonstrated sex and strain×environment interactions such that fewer maladaptive social behaviors were noted in mice that were provided with environmental resources. This association was particularly evident in male mice of both strains in resource-supplemented environments. A small but significant increase in brain weight:body weight ratios occurred in mice in resource-supplemented environments. Under the conditions evaluated here, consistent use of simple environmental resources had a positive long-term effect on the behavioral wellbeing of male and female BALB/c and C57BL/6 mice yet minimally affected other aspects of murine physiology and neuroanatomy.

Intrahepatic Vascular Anatomy in Rats and Mice--Variations and Surgical Implications.

INTRODUCTION: The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. We performed a detailed anatomical imaging study in rats and mice to allow for further refinement of experimental surgical approaches. METHODS: LEWIS-Rats and C57Bl/6N-Mice were subjected to ex-vivo imaging using µCT. The image data were used for semi-automated segmentation to extract the hepatic vascular tree as prerequisite for 3D visualization. The underlying vascular anatomy was reconstructed, analysed and used for determining hepatic vascular territories. RESULTS: The four major liver lobes have their own lobar portal supply and hepatic drainage territories. In contrast, the paracaval liver is supplied by various small branches from right and caudate portal veins and drains directly into the vena cava. Variations in hepatic vascular anatomy were observed in terms of branching pattern and distance of branches to each other. The portal vein anatomy is more variable than the hepatic vein anatomy. Surgically relevant variations were primarily observed in portal venous supply. CONCLUSIONS: For the first time the key variations of intrahepatic vascular anatomy in mice and rats and their surgical implications were described. We showed that lobar borders of the liver do not always match vascular territorial borders. These findings are of importance for the design of new surgical procedures and for understanding eventual complications following hepatic surgery.

Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex.

The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on "full" human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of "full" human neuron morphologies and present direct evidence that human neurons are not "scaled-up" versions of rodent or macaque neurons, but have unique structural and functional properties.

Right Ventricular Epicardial Fibrosis in Mice With Sternal Segment Dislocation.

We report coincident sternal segment dislocation and focally extensive right ventricular epicardial fibrosis observed during routine histopathology evaluation of C57BL/6N mice as part of a high throughput phenotyping screen conducted between 4 and 16 weeks of age. This retrospective case series study was conducted to determine whether cardiac fibrosis was a pathological consequence of sternal segment dislocation. We identified sternal segment dislocation in 51 of the total 1103 mice (4.6%) analyzed at 16 weeks of age. Males were more frequently affected. In all cases but 2, the dislocation occurred at the fourth intersternebral joint. In 42 of the 51 cases (82.4%), the dislocation was encased by regenerative cartilaginous callus that protruded internally into the thoracic cavity (intrathoracic callus) and/or externally to the outer aspect of the sternum (extrathoracic callus). Displacement of dislocated ends of the sternum into the thoracic cavity was present in 19 of 51 cases (36.5%). Coincident minimal or mild right ventricular epicardial and subepicardial fibrosis was observed in 22 of the 51 cases (43%) but was not observed in any of the mice in the absence of sternal segment dislocation. Our data suggest that right ventricular fibrosis was likely caused by direct injury of the right ventricle by the dislocated ends of the sternum and/or by intrathoracic callus that develops post dislocation. Potential pathogenesis for the sternal and cardiac lesions and their implication for the interpretation of phenotypes in mouse models of cardiopulmonary and skeletal disease are discussed.

Retinal projections in the short-tailed fruit bat, Carollia perspicillata, as studied using the axonal transport of cholera toxin B subunit: Comparison with mouse.

To provide a modern description of the Chiropteran visual system, the subcortical retinal projections were studied in the short-tailed fruit bat, Carollia perspicillata, using the anterograde transport of eye-injected cholera toxin B subunit, supplemented by the silver-impregnation of anterograde degeneration following eye removal, and compared with the retinal projections of the mouse. The retinal projections were heavily labeled by the transported toxin in both species. Almost all components of the murine retinal projection are present in Carollia in varying degrees of prominence and laterality. The projections: to the superior colliculus, accessory optic nuclei, and nucleus of the optic tract are predominantly or exclusively contralateral; to the dorsal lateral geniculate nucleus and posterior pretectal nucleus are predominantly contralateral; to the ventral lateral geniculate nucleus, intergeniculate leaflet, and olivary pretectal nucleus have a substantial ipsilateral component; and to the suprachiasmatic nucleus are symmetrically bilateral. The retinal projection in Carollia is surprisingly reduced at the anterior end of the dorsal lateral geniculate and superior colliculus, suggestive of a paucity of the relevant ganglion cells in the ventrotemporal retina. In the superior colliculus, in which the superficial gray layer is very thin, the projection is patchy in places where the layer is locally absent. Except for a posteriorly located lateral terminal nucleus, the other accessory optic nuclei are diminutive in Carollia, as is the nucleus of the optic tract. In both species the cholera toxin labeled sparse groups of apparently terminating axons in numerous regions not listed above. A question of their significance is discussed.