Benavides, Fernando

Benavides, Fernando D.V.M., Ph.D., DACLAM

Selected Publications  |  Search PubMed  |  Contact

Research Interests

Mouse genetics, cancer susceptibility genes, mouse models with epidermal and hair follicle defects

Current Research

The overall goal of my research is to define new mouse models of cancer and to study the genetics of carcinogenesis. As part of this research effort, we developed a new model for the genetic analysis of susceptibility genes using SENCARB/Pt and SSIN mice, two inbred strains derived from the outbred SENCAR stock. Interestingly, we have observed that the treatment of SENCARB/Pt with N-methyl-N-nitrosourea (MNU) results in the induction of a high incidence (> 90%) of thymic lymphomas, whereas SSIN mice are completely resistant, supporting the idea that the differential susceptibility to chemical carcinogenesis is not restricted to the skin model. With the purpose of investigating the genetic basis for the differential susceptibility we make use of hybrid F1, F2, and backcross mice. Linkage analysis is now in progress in order to identify putative quantitative trait loci (QTLs).

As part of a positional cloning and phenotyping project, we have been studying spontaneous mouse mutations with skin phenotypes, trying to identify genes important for skin and hair follicle biology. Our ultimate goal is to develop new animal models of skin inflammation and cancer. As part of these studies we have shown that one of theses mutations (nackt) comprises a deletion in the cathepsin L gene (Immunogenetics 2001, Am. J. Pathol, 2002), and found that CTSL is important for hair follicle morphogenesis and epidermal differentiation. Using this model, we found a paradoxical protective role of CTSL in mouse skin carcinogenesis. We obtained “in vivo” evidence that skin tumorigenesis is enhanced in the absence of CTSL and that a decreased keratinocyte transit of initiated cells is responsible for the increased papilloma formation in the nackt model. In addition, we have successfully identify the luca mutation (loss of hair and irritated skin) as a premature stop codon in the Zdhhc13 gene. This is the first animal model related with a defect in a protein palmitoyl acyltransferase. We have also recently identified another spontaneous recessive mutation (barthez) that affects the Ass1 (argininosuccinate synthetase 1) gene. The phenotype of homozygous mice includes severe retardation in post-natal development, alopecia with scaly skin, ataxia and circling behavior, a complex phenotype that is virtually identical to the human Citrullinemia type I, a rare inherited disorder caused by deficiency of the ASS enzyme. Another project deals with the development of a new genetically defined hairless inbred strain (SKHIN). This will represent a unique tool for the study of the underlying genetic basis of UV-induced skin carcinogenesis. All these projects involve collaborations with Claudio Conti, John DiGiovanni, Susan Fischer, and David Johnson (MDACC Carcinogenesis Department), and with the Pasteur Institute in France.

As the Director of the Animal Genetics Service of the CCSG Research Animal Support Facility – Smithville, I advise and coordinate speed congenics projects, genetic monitoring, background characterizations, and whole genome scans for UMDACC faculty.

Selected Publications

  1. Rojas P, Cadenas MB, Lin PC, Benavides F, Conti CJ, Rodriguez-Puebla ML. Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis, Oncogene, 26 (12), 1723-30, 2007
  2. Benavides F, Gomez G, Venables-Griffith A, Lambertz I, Flores M, Angel JM, Fuchs-Young R, Richie ER, Conti CJ. Differential susceptibility to chemically induced thymic lymphomas in SENCARB and SSIN inbred mice, Mol Carcinog, 45 (7), 543-8, 2006
  3. Kim E, Rundhaug JE, Benavides F, Yang P, Newman RA, Fischer SM. An antitumorigenic role for murine 8S-lipoxygenase in skin carcinogenesis, Oncogene, 24 (7), 1174-87, 2005
  4. Bourgade F, Montagutelli X, Bigbee C, Weiss A, Rigottier-Gois L, Conti CJ, Benavides F. Simple duplex fecal PCR assay that allows identification of false-negative results in Helicobacter sp.-infected mice, Comp Med, 54 (5), 528-32, 2004
  5. Benavides F, Conti CJ, LaCava M, Flores M, Glasscock E, Sternik G, Gimenez-Conti IB, Johnston DA, Dunsford HA, Goldstein LS, Rodriguez LV. Loss of heterozygosity analysis of mouse pulmonary adenomas induced by coal tar, Environ Mol Mutagen, 41 (4), 300-8, 2003
  6. Benavides F, Starost MF, Flores M, Gimenez-Conti IB, Guenet JL, Conti CJ. Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation, Am J Pathol, 161 (2), 693-703, 2002
  7. Benavides F, Zamisch M, Flores M, Campbell MR, Andrew SE, Angel JM, Licchesi J, Sternik G, Richie ER, Conti CJ. Application of inter-simple sequence repeat PCR to mouse models: Assessment of genetic alterations in carcinogenesis, Genes Chromosomes Cancer, 35 (4), 299-310, 2002

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9343