Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Use of chromosome engineering to model a segmental deletion of chromosome band 7q22 found in myeloid malignancies.

Blood | Jun 3, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20233966

Monosomy 7 and del(7q) are associated with adverse features in myeloid malignancies. A 2.5-Mb commonly deleted segment (CDS) of chromosome band 7q22 is implicated as harboring a myeloid tumor suppressor gene (TSG); however, molecular analysis of candidate TSGs has not uncovered loss of function. To determine whether haploinsufficiency for the 7q22 CDS contributes to myeloid leukemogenesis, we performed sequential gene targeting to flank a region of orthologous synteny on mouse chromosome band 5A3 with loxP sites. We then generated Mx1-Cre, 5A3(fl) mutant mice and deleted the targeted interval in vivo. Although excision was inefficient, we confirmed somatic deletion of the 5A3 CDS in the hematopoietic stem cell compartment. Mx1-Cre, 5A3(fl) mice show normal hematologic parameters and do not spontaneously develop myeloid malignancies. The 5A3(fl) deletion does not cooperate with oncogenic Kras(G12D) expression, Nf1 inactivation, or retroviral mutagenesis to accelerate leukemia development and did not modulate responsiveness to antileukemia drugs. These studies demonstrate that it is feasible to somatically delete a large chromosomal segment implicated in tumor suppression in hematopoietic cell populations in vivo; however, our data do not support the hypothesis that the 7q22/5A3 CDS interval contains a myeloid TSG.

Pubmed ID: 20233966 RIS Download

Mesh terms: Animals | Antineoplastic Agents | Base Sequence | Chromosome Banding | Chromosome Deletion | Chromosome Mapping | Chromosomes, Human, Pair 7 | DNA Primers | Drug Resistance, Neoplasm | Gene Targeting | Genes, Neurofibromatosis 1 | Genes, Tumor Suppressor | Genetic Engineering | Humans | Leukemia, Experimental | Leukemia, Myeloid | Mice | Mice, Inbred C57BL | Mice, Mutant Strains | Mice, Transgenic | Models, Genetic | Mutagenesis, Insertional | Proto-Oncogene Proteins p21(ras) | Recombination, Genetic | Species Specificity

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: P01CA40046
  • Agency: NCI NIH HHS, Id: R37CA72614
  • Agency: NCI NIH HHS, Id: U01CA84221

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.