Abstract
In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic substantia nigra neurons degenerate by postnatal day 20. We have now determined that the total number of dopaminergic neurons in the ventral midbrains of a litter of obligatory homozygous weaver pups and a litter of normal wild-type control pups indicates that no significant differences are present between groups at birth. To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [3H]thymidine autoradiography was combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both groups have the same span of neurogenesis but have statistically different proportions of neurons generated on specific days. In wild-type mice, more than half of the dopaminergic neurons originate on or after embryonic day 12. In contrast, over two-thirds of the surviving dopaminergic neurons in homozygous weaver mice originate on or before embryonic day 11. Our data suggest that the weaver gene does not interfere with the generation of dopaminergic neurons, but it preferentially kills late-generated dopaminergic neurons between birth and postnatal day 20.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9137-9140 |
| Number of pages | 4 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 92 |
| Issue number | 20 |
| DOIs | |
| State | Published - Sep 26 1995 |
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Keywords
- [H]thymidine autoradiography
- animal models
- neurogenesis
- neurological mutants
- tyrosine hydroxylase immunocytochemistry
ASJC Scopus subject areas
- Genetics
- General
Cite this
Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice. / Bayer, Shirley A.; Wills, Katherine V.; Triarhou, Lazaros C.; Verina, Tatyana; Thomas, James D.; Ghetti, Bernardino.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 20, 26.09.1995, p. 9137-9140.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Selective vulnerability of late-generated dopaminergic neurons of the substantia nigra in weaver mutant mice
AU - Bayer, Shirley A.
AU - Wills, Katherine V.
AU - Triarhou, Lazaros C.
AU - Verina, Tatyana
AU - Thomas, James D.
AU - Ghetti, Bernardino
PY - 1995/9/26
Y1 - 1995/9/26
N2 - In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic substantia nigra neurons degenerate by postnatal day 20. We have now determined that the total number of dopaminergic neurons in the ventral midbrains of a litter of obligatory homozygous weaver pups and a litter of normal wild-type control pups indicates that no significant differences are present between groups at birth. To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [3H]thymidine autoradiography was combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both groups have the same span of neurogenesis but have statistically different proportions of neurons generated on specific days. In wild-type mice, more than half of the dopaminergic neurons originate on or after embryonic day 12. In contrast, over two-thirds of the surviving dopaminergic neurons in homozygous weaver mice originate on or before embryonic day 11. Our data suggest that the weaver gene does not interfere with the generation of dopaminergic neurons, but it preferentially kills late-generated dopaminergic neurons between birth and postnatal day 20.
AB - In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic substantia nigra neurons degenerate by postnatal day 20. We have now determined that the total number of dopaminergic neurons in the ventral midbrains of a litter of obligatory homozygous weaver pups and a litter of normal wild-type control pups indicates that no significant differences are present between groups at birth. To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [3H]thymidine autoradiography was combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both groups have the same span of neurogenesis but have statistically different proportions of neurons generated on specific days. In wild-type mice, more than half of the dopaminergic neurons originate on or after embryonic day 12. In contrast, over two-thirds of the surviving dopaminergic neurons in homozygous weaver mice originate on or before embryonic day 11. Our data suggest that the weaver gene does not interfere with the generation of dopaminergic neurons, but it preferentially kills late-generated dopaminergic neurons between birth and postnatal day 20.
KW - [H]thymidine autoradiography
KW - animal models
KW - neurogenesis
KW - neurological mutants
KW - tyrosine hydroxylase immunocytochemistry
UR - http://www.scopus.com/inward/record.url?scp=0029047356&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029047356&partnerID=8YFLogxK
U2 - 10.1073/pnas.92.20.9137
DO - 10.1073/pnas.92.20.9137
M3 - Article
C2 - 7568088
AN - SCOPUS:0029047356
VL - 92
SP - 9137
EP - 9140
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 20
ER -