Age-dependent accumulation of hybrid vasopressin-oxytocin gene products but not hybrid oxytocin-vasopressin products in the endoplasmic reticulum of Brattleboro rats.
The age-dependence of the incidence of magnocellular neurosecretory neurons containing abnormal accumulations of peptide in the rough endoplasmic reticulum was examined in homozygous Brattleboro rats and in their wild-type Long Evans counterparts. Neurons in which the immunophenotype of the peptide aggregates indicate that somatic cross-over mutations involving the 5' end of the vasopressin gene and the 3' end of the oxytocin gene have occurred, increased with age in homozygous Brattleboro rats, reaching a maximum of 24 cells per hypothalamus (approximately 0.6% of the vasopressin neurons). The increase occurred in both male and female animals but was significantly greater in females. The average incidence of such cells was 6 times greater in the supraoptic than in the paraventricular nucleus. No such cells could be detected in either nucleus of Long Evans rats despite the evidence for hybrid mRNA in these animals. Moreover, no accumulation of peptide translated from the hybrid mRNAs derived from the 5' end of the oxytocin gene and the 3' end of the vasopressin gene could be detected in either Brattleboro or Long Evans animals. These results strongly suggest that the accumulation of peptide in the rough endoplasmic reticulum of vasopressin neurons in homozygous Brattleboro rats is due to an abnormality other than the somatic crossing-over mutation. A second type of abnormal magnocellular neuron with accumulations of peptide in the rough endoplasmic reticulum, in which the immunophenotype of the peptide reveals products derived only from the oxytocin precursor, was present in both Long Evans and Brattleboro rats, but did not increase with age in Brattleboro rats. The incidence of these cells was similar in the supraoptic and paraventricular nuclei.
Budd
T C
TC
Department of Human Anatomy, University of Oxford, UK.
Morris
J F
JF
D000375:Aging; D000818:Animals; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D005260:Female; D006720:Homozygote; D007031:Hypothalamus / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011910:Rats, Brattleboro; D014667:Vasopressins / Q000235:genetics / Q000378:metabolism*
D011498:Protein Precursors; D014667:Vasopressins; D010121:Oxytocin