[Morphologic and functional characteristics of an animal model of cerebellar degeneration (lurcher mutant mice)].

Lurcher mutant mice are characterized by genetically determined degeneration of cerebellar Purkinje cells, granule cells and inferior olivary neurons (ION). In the morphological part of this study Lurcher mutant and wild type mice were given intraperitoneal injections of 3-acetylpyridine (3AP) to look at the effect of this neurotoxin and niacinamide antagonist on the ION. Intraperitoneal administration of 3AP is characterized by the different sensitivity of ION in Lurcher mutant mice and wild type mice in both infant and young adult animals.

The effect of 3-acetylpyridine on inferior olivary neuron degeneration in Lurcher mutant and wild-type mice.

Lurcher mutant and wild-type mice were given intraperitoneal injections of 3-acetylpyridine to look at the toxic effects of this drug on the inferior olivary neurons. Intraperitoneal administration of 3-acetylpyridine is characterized by the different sensitivity of inferior olivary neurons in Lurcher mutant and wild-type mice. Lurcher mutants suffered a destruction of these neurons while wild-type mice were unaffected.

Carbonic anhydrase II and carbonic anhydrase-related protein in the cerebellar cortex of normal and lurcher mice.

The developmental profiles of carbonic anhydrase II (CA-II) and a carbonic anhydrase related protein (CARP) were studied in rat and mouse cerebella. Enzyme histochemistry, immunohistochemistry, in situ hybridisation and Western blotting were used to study the synthesis and expression of these enzymes in cerebellar sections from age matched control, CA-II deficient and lurcher mice, the latter being characterised by Purkinje cell degeneration. Both CA-II and CARP were first found to be expressed in the Purkinje cells in the 9 day old mouse, and the immunoreactivity of both peptides increased with time.

Cerebellar Purkinje cells from the lurcher mutant and wild-type mouse grown in vitro: a light and electron microscope study.

Lurcher is an autosomal semidominant murine mutation. Lurcher heterozygotes (+/Lc) lose all their cerebellar Purkinje cells by adulthood. Explants from 2 days postnatal (P2) wild-type (+/+) and +/Lc cerebellar cortex were grown in vitro to investigate the role of local neuronal environment and afferent input on the degenerating +/Lc Purkinje cell.

The nucleus is insulated from large cytosolic calcium ion changes.

Extracellular events regulate functions in the cell nucleus by means of calcium ions acting through effector enzymes. Recently, the traditional view of the nuclear pore as freely permeable to small ions has been questioned as a result of reports that nuclear calcium can be regulated independently of cytosolic calcium. We have used confocal microscopy of fluorescent Ca2+ indicators to investigate the Ca2+ dynamics between cytosol and nucleus in neurons.

The fine structure of the Purkinje cell and its afferents in lurcher chimeric mice.

Lurcher is an autosomal dominant mutation in the mouse. Heterozygote (+/Lc) animals lose 100% of their cerebellar Purkinje cells during the first postnatal month. Aggregation chimeras made between +/Lc and wild-type embryos have been used to demonstrate that this neuronal cell death is a cell autonomous property of the +/Lc Purkinje cells.

Studies of the dendritic tree of wild-type cerebellar Purkinje cells in lurcher chimeric mice.

Naturally occurring mutations are valuable tools for the study of neural development, especially when used in conjunction with the techniques of chimeric mouse production. In this study we examine the response of Purkinje cell dendrites to the altered developmental environment found in the lurcher in equilibrium with wild-type chimera. Lurcher (+/Lc) is an autosomal dominant gene that causes the cell-autonomous degeneration of all Purkinje cells of +/Lc genotype.

Biophysical studies of the cellular elements of the rabbit carotid body.

The carotid body is a major sensor of oxygen partial pressure in the arterial blood, and plays a role in the control of respiration. Despite extensive investigation of the structure, the cellular basis of the transduction mechanism remains poorly understood. We have developed a preparation of freshly dissociated cells from the rabbit carotid body, in which two cell types may be identified using morphological criteria.

Purkinje cells and granule cells in the cerebellum of the Stumbler mutant mouse.

The lesion in a new neurologically mutant mouse, Stumbler, has been studied using a Golgi technique and electron microscopy. Heterozygote Stumbler mice have smaller cerebella than their normal littermates from the earliest age studied (9 days postnatal). Purkinje cells have small immature-looking dendritic trees and retain somatic spines for up to 14 days longer than in normal mice.

Stumbler, a new mutant mouse with cerebellar disease.

A new mutant mouse named Stumbler (stu) displays clinical features suggesting a cerebellar lesion. The main light microscopic findings, based on a Golgi technique and on sections of plastic embedded material, are that Purkinje cells in the mutant cerebellum have small dendritic arborizations and exhibit immature spines on their somata. Purkinje cells also contain an increased number of mitochondrial profiles both in cell bodies and in swellings on dendrites.

The identification of mossy fibres and their cells of origin in the normal and Lurcher mutant mouse.

The behavioural mutant mouse Lurcher survives to adult life as the heterozygote (Lc/+) and shows a disorder of gait. The neurological lesion has been shown to involve degeneration of Purkinje cells and inferior olivary neurones (Caddy and Biscoe 1976). It follows that the climbing fibre input is reduced and we wished to know if the mossy fibre input was also affected.

Electrophysiological studies on interpositus neurones in the normal and Lurcher mutant mouse.

The response characteristics of interpositus neurones (IP) to sciatic nerve stimulation were studied in normal and Lurcher mutant mice under pentobarbitone anaesthesia. The response of IP neurones in the normal mouse was a short latency bimodal excitation (E1-I1-E2) followed by a depression of the firing rate (I2) and ending with a longer latency excitation (E3) which was completed within 225 msec. The response of the majority of IP neurones in the Lurcher mouse was a short latency unimodal excitation (LE1) which corresponded in time to the E1-I1-E2 phase in the normal.

Numbers and diameters of motoneurons and myelinated axons in the facial nucleus and nerve of the albino rat.

The number and diameter of the motoneurons in serial sections of the facial nucleus in the albino rat were estimated using a photograph-camera lucida technique for counting and measuring cells in conjunction with a systematic section method for sampling the population. The mean diameter of facial motoneuron nucleoli was also estimated. Total cell counts were estimated using two formulas, one a basic count and the other the basic count corrected for split nucleoli errors.

Investigation of cranial and other nerves in the mouse with muscular dystrophy.

In the muscular dystrophic mouse mutant there is an absence of Schwann cells over circumscribed lengths of all cranial nerves except for II (I was not examined) and the lesion involves the sympathetic system. Where present, Schwann cells do not produce myelin of normal thickness. The lesion is similar to that described for the spinal roots.