Abstract
Xiphophorus fishes and their hybrids are used as models for the study of melanoma and other diseases. The cyclin-dependent kinase inhibitor gene family in humans is comprised of four members, including CDKN2A (P16), and dysregulation of this gene is implicated in numerous neoplasms including melanomas. We have investigated the status of the gene family in the southern platyfish X. maculatus. Xiphophorus harbors at least two such loci, which we now term CDKN2A/B and CDKN2D. Both loci map to Xiphophorus linkage group 5, a genomic area that has long been known to harbor the DIFF tumor suppressor locus. Within this report, we report on the complete cloning, genomic exon/intron boundary delineation, linkage mapping and expressional characteristics of Xiphophorus CDKN2D. We also compare and contrast this expression to that of the previously isolated CDKN2AB locus in normal and neoplastic tissues derived from non-hybrid and hybrid fishes. The hypothetical evolutionary relationships of gene family members and their involvement in melanoma is evaluated. In comparison to CDKN2A/B, the RNA expression of Xiphophorus CDKN2D differs in normal tissues and is not associated with melanotic/pathologic tissues, confirming functional divergence between obvious homologues.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 291-299 |
| Number of pages | 9 |
| Journal | Comparative Biochemistry and Physiology - C Toxicology and Pharmacology |
| Volume | 138 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 2004 |
| Externally published | Yes |
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Keywords
- Cell cycle
- INK4
- Melanoma
- Platyfish
- Swordtail
- Teleost
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Health, Toxicology and Mutagenesis
- Pharmacology
Cite this
Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes. / Kazianis, Steven; Khanolkar, Vandeeta A.; Nairn, Rodney S.; Rains, J. Douglas; Trono, David; Garcia, Rachel; Williams, Earlanda L.; Walter, Ronald B.
In: Comparative Biochemistry and Physiology - C Toxicology and Pharmacology, Vol. 138, No. 3, 07.2004, p. 291-299.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes
AU - Kazianis, Steven
AU - Khanolkar, Vandeeta A.
AU - Nairn, Rodney S.
AU - Rains, J. Douglas
AU - Trono, David
AU - Garcia, Rachel
AU - Williams, Earlanda L.
AU - Walter, Ronald B.
PY - 2004/7
Y1 - 2004/7
N2 - Xiphophorus fishes and their hybrids are used as models for the study of melanoma and other diseases. The cyclin-dependent kinase inhibitor gene family in humans is comprised of four members, including CDKN2A (P16), and dysregulation of this gene is implicated in numerous neoplasms including melanomas. We have investigated the status of the gene family in the southern platyfish X. maculatus. Xiphophorus harbors at least two such loci, which we now term CDKN2A/B and CDKN2D. Both loci map to Xiphophorus linkage group 5, a genomic area that has long been known to harbor the DIFF tumor suppressor locus. Within this report, we report on the complete cloning, genomic exon/intron boundary delineation, linkage mapping and expressional characteristics of Xiphophorus CDKN2D. We also compare and contrast this expression to that of the previously isolated CDKN2AB locus in normal and neoplastic tissues derived from non-hybrid and hybrid fishes. The hypothetical evolutionary relationships of gene family members and their involvement in melanoma is evaluated. In comparison to CDKN2A/B, the RNA expression of Xiphophorus CDKN2D differs in normal tissues and is not associated with melanotic/pathologic tissues, confirming functional divergence between obvious homologues.
AB - Xiphophorus fishes and their hybrids are used as models for the study of melanoma and other diseases. The cyclin-dependent kinase inhibitor gene family in humans is comprised of four members, including CDKN2A (P16), and dysregulation of this gene is implicated in numerous neoplasms including melanomas. We have investigated the status of the gene family in the southern platyfish X. maculatus. Xiphophorus harbors at least two such loci, which we now term CDKN2A/B and CDKN2D. Both loci map to Xiphophorus linkage group 5, a genomic area that has long been known to harbor the DIFF tumor suppressor locus. Within this report, we report on the complete cloning, genomic exon/intron boundary delineation, linkage mapping and expressional characteristics of Xiphophorus CDKN2D. We also compare and contrast this expression to that of the previously isolated CDKN2AB locus in normal and neoplastic tissues derived from non-hybrid and hybrid fishes. The hypothetical evolutionary relationships of gene family members and their involvement in melanoma is evaluated. In comparison to CDKN2A/B, the RNA expression of Xiphophorus CDKN2D differs in normal tissues and is not associated with melanotic/pathologic tissues, confirming functional divergence between obvious homologues.
KW - Cell cycle
KW - INK4
KW - Melanoma
KW - Platyfish
KW - Swordtail
KW - Teleost
UR - http://www.scopus.com/inward/record.url?scp=7944234073&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7944234073&partnerID=8YFLogxK
U2 - 10.1016/j.cca.2004.08.003
DO - 10.1016/j.cca.2004.08.003
M3 - Article
C2 - 15533787
AN - SCOPUS:7944234073
VL - 138
SP - 291
EP - 299
JO - Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology
JF - Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology
SN - 0742-8413
IS - 3
ER -