In:
Cells Tissues Organs, S. Karger AG, Vol. 150, No. 3 ( 1994), p. 159-169
Abstract:
Trisomy 19 (Tsl9), the only murine trisomy compatible with survival beyond birth, allows systematic studies on the effect of an additional chromosome upon postnatal development. In this review, developmental consequences of murine Tsl9 are presented. In Tsl9 mice, viability is limited to a few weeks postpartum. Body weight is markedly reduced. The occurrence of malformations of the cardiovascular, skeletal and central nervous systems depends on the parental genetic background. In all organ systems examined, development is delayed by 1-2 days. Tsl9 hematopoietic cells exhibit the same survival rate in lethally irradiated hosts as controls. In the CNS, morphological and morphometric studies fail to detect cytoarchitectonic abnormalities: the orderly pattern of development is not disturbed in the visual cortex, cerebellum, locus coeruleus (LC), optic nerve and retina; but neurogenesis, gliogenesis, myelination and invasion of blood vessels are each delayed by 1-2 days. In addition, size and cell number of different brain regions are reduced to a variable degree: the telencephalon and the cerebellar vermis are markedly hypoplastic, whereas the LC, the optic nerve and the retina are hardly reduced in size. Choline acetyltransferase activity is selectively reduced in the Tsl9 telencephalon, whereas the activity of the marker enzyme of the GABAergic system is decreased in all brain regions examined. In behavioral tests, visual capacities and orientation ability of Tsl9 mice develop with a 2-day delay, while motor coordination is more severely retarded; there is no response to auditory stimulation. Fetal Tsl9 ovaries show excessive oocyte degeneration. Development of the testes is only disturbed postnatally: differentiation of gonocytes to A spermatogonia and formation of B spermatogonia are severely disrupted, resulting in a striking reduction in germ cell number and a predominance of Sertoli cells. Histopathological changes exhibit marked intra-and interindividual variations. In addition, growth and lumen formation are impaired in the seminiferous tubules. The proliferative capacity of cultured Tsl9 cells is not altered. The activities of glutamate oxaloacetate transaminase-1 and phosphoglycerate mutase-1 are increased by 50%, compatible with a gene dosage effect of these two enzymes. Ganglioside composition is altered in the Tsl9 liver, but not in the brain, spleen and heart. Two-dimensional protein patterns show both chromosome-specific and chromosome-nonspecific changes, their frequency being far lower than expected from the number of proteins coded on chromosome 19. Possible pathogenetic mechanisms are discussed.
Type of Medium:
Online Resource
ISSN:
1422-6405
,
1422-6421
Language:
English
Publisher:
S. Karger AG
Publication Date:
1994
detail.hit.zdb_id:
1481840-1
SSG:
12
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