Altered development of dopaminergic cells in the retina of weaver mice

Abstract

Postnatal degeneration of dopaminergic (DA) cells is known to occur in mesencephalic nuclei of mutant weaver mice, whereas retinal DA content is reported to be unchanged in the adult animal. To determine whether morphological changes occur in the weaver retinal DA system, we compared weaver and control developing and adult retinas after tyrosine hydroxylase (TH) immunohistochemistry. The density and distribution of DA cells were analyzed using Dirichlet tessellation. Not only was no DA cell loss found in adult weaver retinas, but we even observed an increase in DA cells in weaver compared to control retinas between postnatal days 14 and 30. Furthermore, some unusual features were found during the latter period: atypical cells (representing a maximum of 12% of the whole DA cell population) were observed, and these differed from typical DA cells in terms of both location (slightly more external within the inner nuclear layer) and appearance (flat somata, round and clear nuclei, thick dendritic trunks emerging laterally and giving rise to horizontal processes). Some of the atypical cells were intermingled in a delicate network lying in a more outer focal plane than the main DA plexus. The expression of GIRK2, a G protein‐related inward rectifying K+ channel responsible for the weaver syndrome, was investigated. Although no GIRK2 labeling was demonstrated in DA cells, its possible involvement in the transient disturbances observed in the weaver DA retinal system is discussed. J. Comp. Neurol. 412:656–668, 1999. © 1999 Wiley‐Liss, Inc.

From mice to men: lessons from mutant ataxic mice

“…In the hippocampus of homozygous Weaver mice, a thicker pyramidal cell layer in the CA3 area with cell-free spaces, ectopic clusters of pyramidal cells, on occasions subdivision of the pyramidal cell layer into 2–3 layers and disorganized mossy fiber projections have been described [ 141 ]. The retinas of adult Weaver mice contain more dopaminergic cells, some of which have an abnormal appearance and location [ 142 ]. Retinopetal tyrosine hydroxylase-immunoreactive fibers are also dramatically increased in number [ 143 ].…”

Morphology of dopaminergic amacrine cells in the mouse retina: Independence from homotypic interactions

“…Despite comprising such a tiny minority of all retinal cells, the total number of DA cells in the mouse retina is tightly regulated, exhibiting minimal variation within a given strain of mice despite large inter-strain differences (Whitney et al, 2009). These cells are distributed equally across the four quadrants of the mouse retina (Savy et al, 1999), but their local distribution has been variously described as "regularly ordered" (Wulle and Schnitzer, 1989), "irregular" (Gustincich et al, 1997), or "randomly distributed" (Versaux-Botteri et al, 1984). They have been shown to be modelled by distributions of randomly assigned cells that are precluded from being positioned in close proximity to neighboring like-type cells, capturing the essence of how these mosaics differ from truly random distributions of cells while appearing highly irregular (Raven et al, 2003; see also Mariani et al, 1984).…”

GIRK2 and neuronal pattern of generation and settling in homozygous <em>weaver</em> mice

“…19,20 Nevertheless, variations in the number of dopaminergic (DA) neurons have been reported in the wv/wv retina during development. 21 The weaver homozygotes were originally identified at the Jackson Laboratories based on their instability of gait, the most obvious behavioral abnormality, hence the origin of the name weaver. In mice, gait abnormalities generally imply cerebellar defects and, for many years, study of the pathology disturbance caused by GIRK2wv focused entirely on the cerebellum.…”