Human homologs of two testes-expressed loci on mouse chromosome 17 map to opposite arms of chromosome 6

Bibbins, K B; Tsai, Jen-Yue; Schimenti, John C.; Sarvetnick, Nora; Zoghbi, Huda Y.; Goodfellow, Peter N.; Silver, Lee M.

doi:10.1016/0888-7543(89)90098-0

Cited by 28 publications

(8 citation statements)

References 15 publications

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“…Interestingly, our previous studies also demonstrated that the transgene was expressed in the testes and prostate of monotransgenic mice that contained only the mutant Ki-ras allele and lacked the tet transactivator protein, although there were no morphological changes observed in either organ. The human homologs of two testes-expressed loci found on human chromosome 17 (Bibbins et al, 1989), as well as an additional gene that plays a role in spermatogenesis (Bryan, 1977), have been shown to map to opposite arms of mouse chromosome 6, which may explain these earlier observations (Floyd et al, 2005).…”

Section: Effects Of Mutant Ras Gene Dosage On Tumor Phenotypesupporting

confidence: 67%

Effects of mutant human Ki-rasG12C gene dosage on murine lung tumorigenesis and signaling to its downstream effectors

Dance-Barnes

Kock

Floyd

et al. 2008

Toxicology and Applied Pharmacology

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Studies in cell culture have suggested that the level of RAS expression can influence the transformation of cells and the signaling pathways stimulated by mutant RAS expression. However, the levels of RAS expression in vivo appear to be subject to feedback regulation, limiting the total amount of RAS protein that can be expressed. We utilized a bitransgenic mouse lung tumor model that expressed the human Ki-ras G12C allele in a tetracycline-inducible, lung-specific manner. Treatment for 12 months with 500 μg/ml of doxycycline (DOX) allowed for maximal expression of the human Ki-ras G12C allele in the lung, and resulted in the development of focal hyperplasia and adenomas. We determined if different levels of mutant RAS expression would influence the phenotype of the lung lesions. Treatment with 25, 100 and 500 μg/ml of DOX resulted in dosedependent increases in transgene expression and tumor multiplicity. Microscopic analysis of the lungs of mice treated with the 25 μg/ml dose of DOX revealed infrequent foci of hyperplasia, whereas mice treated with the 100 and 500 μg/ml doses exhibited numerous hyperplastic foci and also adenomas. Immunohistochemical and RNA analysis of the downstream effector pathways demonstrated that different levels of mutant RAS transgene expression resulted in differences in the expression and/or phosphorylation of specific signaling molecules. Our results suggest that the molecular alterations driving tumorigenesis may differ at different levels of mutant Ki-ras G12C expression, and this should be taken into consideration when inducible transgene systems are utilized to promote tumorigenesis in mouse models.

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Section: Effects Of Mutant Ras Gene Dosage On Tumor Phenotypesupporting

confidence: 67%

Effects of mutant human Ki-rasG12C gene dosage on murine lung tumorigenesis and signaling to its downstream effectors

Dance-Barnes

Kock

Floyd

et al. 2008

Toxicology and Applied Pharmacology

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“…2). The mouse Pgk2 gene is located distal to the Mhc, whereas the human counterpart, PGKlP2, was mapped centromeric to the Mhc region (BIBBINS et al 1989;BLANCHE et al 1991). Hence, the breakpoint of conserved synteny between mouse and human is between Leh89 and Pgk2 in mouse and may correspond to In(l7)4d.…”

Section: Evolutionary Breakpoints For Conserved Syntenymentioning

confidence: 99%

Genomic Evolution of the Distal Mhc Class I Region on Mouse Chr 17

et al. 2004

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A 5-Mb YAC contig, partly supplemented with BAC contigs, was created from the distal Mhc class I region on mouse Chr 17. The gene order of Znf173-Tctex5-Mog-D17Tu42-D17Leh 89 is conserved between mouse and human but not the physical distance, supporting the independent expansion of Mhc class I genes in the so-called accordion model of Mhc evolution. The distal H2-M region includes the breakpoint of conserved synteny between mouse and human as well as the In(17)4 t-inversion. The H2-M region is rich in L1 repeats, implying that the insertion of L1 repeats may be associated with the evolutionary flexibility to break a chromosome.

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“…75 The TCP1, TCP10, superoxide dismutase (SOD2), insulin-like growth factor type-2 receptor (IGF2R) and plasminogen (PLG) genes map in the human to chromosome 6q21-q27, whereas they map to the proximal end of chromosome 1 7 in the mouse. 7°, 74-7~ It seems that the human counterpart of the mouse t-complex has been split into two regions: the proximal segment of the t-complex has moved to the 6q, while the distal segment has remained on the 6p (Figure 2).…”

Section: Chromosome 6: Human T-complex?mentioning

confidence: 99%

Major histocompatibility complex, t-complex, and leukemia

Dorak

Burnett

1992

Cancer Causes Control

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In experimental models, leukemia was the first disease shown to have an association with the major histocompatibility complex (MHC) genes. In humans, several allelic human-leukocyte antigen (HLA) associations also have been recognized. In addition to allelic associations, atypical HLA segregation patterns have been observed in leukemic families. These include a higher frequency of HLA-identical unaffected siblings, increased HLA homozygosity and increased maternal HLA-DR identity. These observations suggest preferential transmission of disease-associated haplotypes and a male transmission bias in leukemic families. The lack of disease-specific segregation, however, supports the idea that the HLA system is not directly relevant in leukemogenesis. Therefore, the existence of another genetic region linked to the MHC, causing segregation distortion, and containing recessive leukemia susceptibility genes may be postulated. The mouse t-complex would fit this model. This gene complex has recessive (semi-) lethal genes, is transmitted preferentially through fathers, and both the mouse t-complex and its rat homolog, growth and reproduction complex grc, confer susceptibility to carcinogenesis. This model could also explain the increased spontaneous abortion rate in mothers of leukemic patients, epidemiologic associations of leukemia with oral clefts and neuroectodermal tumors, and the transmission of a radiation-induced leukemia risk through fathers. Such segregation distortion might be the reason behind the maintenance of a gene(s) with a lethal effect in the population.

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Human homologs of two testes-expressed loci on mouse chromosome 17 map to opposite arms of chromosome 6

Cited by 28 publications

References 15 publications

Effects of mutant human Ki-rasG12C gene dosage on murine lung tumorigenesis and signaling to its downstream effectors

Effects of mutant human Ki-rasG12C gene dosage on murine lung tumorigenesis and signaling to its downstream effectors

Genomic Evolution of the Distal Mhc Class I Region on Mouse Chr 17

Major histocompatibility complex, t-complex, and leukemia

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