Biomedical subjects

N J Mangini

Publications and source records attributed to N J Mangini.

25 records · Page 2Linked to original sources

PubMed1985

The optokinetic nystagmus and ocular pigmentation of hypopigmented mouse mutants.

We tested the optokinetic nystagmus (OKN) reflex of various hypopigmented mutant mice and ultrastructurally examined the pigmentation of various ocular structures in these mutants. Using electron microscopy we examined the pigmentation of the choroid and retinal pigment epithelium (RPE) and measured the numerical density, volume density, and distribution of RPE melanosomes of mice with the following phenotypes: (1) wild type, (2) mutants that have abnormal or no OKN in response to horizontally moving, full-field stimulation, and (3) other mutants that have normal OKN but reduced choroidal pigmentation. We also measured the OKN of all these mice in response to horizontally moving stimuli that were restricted to the nasal or to the temporal retina. We found that in the mutants with normal OKN the numerical density of melanosomes in the RPE was within the range found for wild type, while the numerical density was reduced for the mutants with abnormal OKN. For one mutant with normal RPE pigmentation and normal OKN, the choroidal pigmentation was nearly absent. For the genotypes with abnormal OKN the volume density of the RPE melanosomes and percent apical melanosomes were sometimes greater and sometimes less than normal. The OKN patterns of these mice fell into the following categories: (1) wild type; (2) field-restriction dependent OKN with small following movements but no OKN in response to full-field stimulation, normal OKN in response to stimulation of the nasal retina, and OKN of reversed direction in response to stimulation of the temporal retina; (3) oblique with slow oblique following movements and reduced numbers of OKNs with oblique quick phases in response to horizontally moving, full-field stimulation, nearly normal OKN in response to stimulation of the nasal retina, and OKN of reversed direction in response to stimulation of the temporal retina. The horizontal component of the oblique response to full-field stimulation was in the same direction for the two eyes, but the vertical component was in the opposite direction. (4) Slow, small amplitude, with no or very small following movements in response to full-field stimulation, following movements in response to stimulation of the nasal retina and reversed "following" movements in response to stimulation of the temporal retina but few or no quick phases of the OKN for any stimulus condition. These results show that a variety of abnormalities of the OKN occur for hypopigmentation mutants of the mouse.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

Visually evoked eye movements in mouse mutants and inbred strains. A screening report.

The authors screened various inbred strains and mutants of the mouse, Mus musculus, for qualitatively abnormal or reduced numbers of optokinetic nystagmus (OKN) eye movements. Thirteen hypopigmentation mutants and ten neuromuscular mutants were found to have abnormal or markedly reduced OKN, but none of these mutants had retinal degeneration. Ten other hypopigmentation mutants and nine other neuromuscular mutants had relatively normal OKN, thus showing that neither hypopigmentation nor neuromuscular abnormality per se are well-correlated with abnormal OKN. These findings show that many mutants with visual defects are available from existing holdings. These visual mutants may serve as a resource for the study of the function and development of the mammalian visual system.

Animals↗

PubMed1983

Discrete visual defects in pearl mutant mice.

The mutant mouse pearl, characterized by its hypopigmentation, has a specific functional defect in a sensory system--the retina. The intact pearl mouse has reduced sensitivity in the dark-adapted condition. Normal sensitivity is restored by isolation and superfusion of the retina with bicarbonate-buffered Ringer solution, suggesting that the retinal expression of the pearl mutation depends on a diffusible substance. The pearl phenotype is described as a possible model for human congenital stationary night blindness.

Animals↗

PubMed1980

Retinotopic organization of striate and extrastriate visual cortex in the mouse.

Detailed retinotopic maps of primary visual cortex (area 17) and the extrastriate visual regions surrounding it (areas 18a and 18b) have been constructed for the C57BL/6J mouse using standard electrophysiological mapping techniques. Primary visual cortex (area 17), as defined cytoarchitectonically, contains one complete representation of the contralateral visual field, termed V1, in which azimuth and elevation lines are approximately orthogonal. The upper visual field is represented caudally and the nasal field laterally. Binocular cells are encountered in the cortical representation of the nasal 30--40 degrees of the visual field, and there is an expanded representation of the nasal field. Extrastriate visual cortex of the mouse, like that of other mammals, contains multiple representations of the visual field. The cytoarchitectonic region of cortex lateral and rostral to area 17, termed area 18a, contains at least two such representations. The more medial of these, which by convention we have called V2, is a narrow strip surrounding V1 on its lateral and rostral aspects; the vertical meridian lies along a portion of its common border with V1. The visual field representation in V2 is not a mirror image of that in V1; the representation of the horizontal meridian forms the lateral border of V2, and the visual field representation is split so that adjacent points on either side of the horizontal meridian are represented in nonadjacent parts of V2. The other visual field representation within area 18a, which we have termed V3, is a small but apparently complete representation that lies lateral to V2. The visual field representations medial to area 17 correspond to cytoarchitectonic area 18b. Area 18b contains two representations of the temporal visual field that we have labeled Vm-r and Vm-c, and contains little or no representation of the most nasal aspect of the field.

Animals↗

PubMed1980

Laminar distribution of receptive field properties in the primary visual cortex of the mouse.

We studied the receptive field properties of single neurons in the primary visual cortex (area 17) of the mouse and the distribution of receptive field types among the cortical laminae. Three basic receptive field types were found: 1) Cells with oriented receptive fields, many of which could be classified as simple or complex, were found in all layers of the cortex, but occurred with greater frequency in layers II and III and less commonly in Layer IV. 2) Cells with non-oriented receptive fields had ON, OFF, or ON-OFF centers; they were found in all layers but were predominant in layer IV. Two subclasses of non-oriented receptive fields were characterized based on their responses to stationary and moving stimuli. One group of cells with non-oriented receptive fields responded vigorously with sustained firing to stationary flashing stimuli, and also responded well to moving stimuli over a wide range of stimulus velocities. A second group of non-oriented cells, termed motion-selective, responded poorly or not at all to stationary stimuli and responded optimally to moving stimuli over a restricted range of velocities. 3) A distinct group of neurons, termed large field, non-oriented (LFNO) cells, were found almost exclusively in layer V. LFNO cells had receptive fields that were larger than those of the other two major classes at all visual-field locations; they also had higher rates of spontaneous activity and responded to higher stimulus velocities than the other classes. In these respects, LFNO cells resembled the layer V cells of area 17 in the cat and the layer V and VI cells of area 17 in the monkey that project to the superior colliculus. We injected horseradish peroxidase into the superior colliculus, and determined that corticotectal cells in the mouse were also located in layer V, the layer where we recorded LFNO cells. Additional evidence that some LFNO cells project to the superior colliculus was provided by preliminary experiments in which we stimulated the superior colliculus and antidromically activated cortical cells with LFNO receptive fields. Neurons with LFNO receptive fields thus constitute a class that is functionally distinct, with cell bodies that are located in a single layer (V) of area 17 in the mouse.

Animals↗

PubMedDate not supplied

Effect of hydroxylamine on the subcellular distribution of arrestin (S-antigen) in rod photoreceptors.

The immunocytochemical labeling of arrestin (S-antigen) in photoreceptors of the ovine retina was examined following incubation of the retina with hydroxylamine (NH2OH), an agent known to inhibit the phosphorylation of photoactivated rhodopsin. Intact, isolated retinas bathed in medium containing 20 mM NH2OH, or in control medium lacking NH2OH, were maintained in darkness or exposed to bright light for 3 min (dark-adapted and light-adapted conditions, respectively); further incubated in darkness for 10 min; and then fixed and prepared for cryosectioning. Cryosections were incubated with anti-S-antigen monoclonal antibody MAb A2G5; with secondary antibodies that were conjugated with horseradish peroxidase; and with either 3-amino-9-ethyl carbazole or diaminobenzidine as chromogen. Anti-arrestin labeling in cryosections was then analyzed densitometrically using a light-microscopic image processing system. In dark-adapted control retinas, labeling density of the photoreceptor outer segment (OS) layer (0.061 +/- 0.004; average +/- S.E.M.) was less than that of the inner segment (IS) layer (0.138 +/- 0.011). In light-adapted control retinas, OS labeling density (0.139 +/- 0.007) exceeded IS labeling density (0.095 +/- 0.005). Incubation with NH2OH eliminated this light-dependent increase in labeling of the OS relative to that of the IS, i.e. eliminated the increase in relative OS/IS labeling. Densities of labeling were 0.110 +/- 0.006 (OS) and 0.183 +/- 0.006 (IS) in NH2OH-treated dark-adapted retinas vs. 0.078 +/- 0.004 (OS) and 0.182 +/- 0.008 (IS) in NH2OH-treated light-adapted retinas. Anti-arrestin labeling was also examined in retinas that were exposed to 3 min or 13 min of bright light and then immediately fixed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Ocular↗

PubMedDate not supplied

A 221-bp fragment of the mouse opsin promoter directs expression specifically to the rod photoreceptors of transgenic mice.

Mutations in the human rod opsin gene have been shown to segregate with autosomal dominant retinitis pigmentosa (ADRP) and photoreceptor degeneration in transgenic mice. While these degenerations are characterized by the primary degeneration of rods, cones eventually die as well. To determine whether this subsequent cone degeneration is the result of expression of mutant rod opsin in the cones, the retinal cell-type specificity of a 221-bp fragment of the mouse rod opsin promoter was evaluated. Two transgenic mouse lines generated by injecting a fusion gene comprised of a 221-bp fragment of the mouse rod opsin promoter and the simian virus 40 large tumor antigen gene (Tag) were examined. The expression of Tag causes photoreceptor cell degeneration in members of both transgenic lines. However, the two lines differed with respect to the level of Tag expression and the rate and extent of photoreceptor cell degeneration. Immunocytochemical localization of opsin and Tag in surviving photoreceptor cells was determined and the results were confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Rod- and cone-mediated function was evaluated by electroretinography (ERG). In the higher Tag-expressing transgenic line only one row of nuclei remained in the outer nuclear layer at postnatal day (P) 150. While these nuclei showed no antigenicity for rod opsin or Tag, they did stain with an antibody that reacts with both rod and cone S-antigens (arrestins), indicating that these cells were surviving photoreceptor nuclei. Positive staining with peanut agglutinin, which uniquely decorates matrix domains surrounding cones in the normal retina, confirmed that the surviving photoreceptor nuclei were of cone origin. RT-PCR substantiated the results from immunostaining; amplification product was obtained using blue cone opsin transcripts but not from either Tag or rod opsin transcripts. The second transgenic mouse line exhibited a much slower photoreceptor cell death that was associated with low levels of Tag transgene transcript. At P120, approximately 50% of photoreceptors remained and an approximately 45% reduction in the rod ERG a-wave was observed. Cone-mediated ERGs, however, were normal. The results demonstrate the rod-specific expression of Tag as directed by the 221-bp fragment of the mouse rod opsin promoter and suggest that the cone degeneration in ADRP or transgenic mice associated with mutations in the rod opsin gene is a secondary effect of rod degeneration.

Animals↗