Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice.

Lineage-specific regulatory elements can be used to direct expression of a variety of genes to specific tissues in transgenic mice. If the hybrid constructs contain a gene encoding a cytotoxic gene product, then genetic ablation of a specific cell lineage can be achieved. We have generated six transgenic mice by introducing into fertilized eggs the mouse gamma 2-crystallin promoter fused to the coding region of the diphtheria toxin A-chain gene. Three of these mice and all the transgenic offspring analyzed were microphthalmic. The lenses of these mice displayed considerable heterogeneity: some were almost normal morphologically but reduced in size, whereas others were grossly aberrant and deficient in nuclear fiber cells. These studies indicate that programmed ablation of specific cell types can be stably transmitted through the germ line.

[1]  R. Palmiter,et al.  Cell lineage ablation in transgenic mice by cell-specific expression of a toxin gene , 1987, Cell.

[2]  Constance L. Cepko,et al.  A common progenitor for neurons and glia persists in rat retina late in development , 1987, Nature.

[3]  L. Tsui,et al.  In situ detection of beta-galactosidase in lenses of transgenic mice with a gamma-crystallin/lacZ gene. , 1987, Science.

[4]  I. Maxwell,et al.  Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide. , 1986, Cancer research.

[5]  R. Jaenisch,et al.  Retroviruses as probes for mammalian development: Allocation of cells to the somatic and germ cell lineages , 1986, Cell.

[6]  Ihor R. Lemischka,et al.  Developmental potential and dynamic behavior of hematopoietic stem cells , 1986, Cell.

[7]  C. Lo Localization of low abundance DNA sequences in tissue sections by in situ hybridization. , 1986, Journal of cell science.

[8]  G. Keller,et al.  Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors , 1985, Nature.

[9]  J. Dick,et al.  Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice , 1985, Cell.

[10]  W. Gehring The homeo box: A key to the understanding of development? , 1985, Cell.

[11]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[12]  V. Chapman,et al.  Identification of embryonic cell lineages in histological sections of M. musculus↔M. caroli chimaeras , 1983 .

[13]  J Kimble,et al.  Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans. , 1981, Developmental biology.

[14]  P. Thomas,et al.  Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Sulston,et al.  Regulation and cell autonomy during postembryonic development of Caenorhabditis elegans. , 1980, Developmental biology.

[16]  G R Stark,et al.  Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[17]  E. Mekada,et al.  One molecule of diphtheria toxin fragment a introduced into a cell can kill the cell , 1978, Cell.

[18]  J. Mcavoy Cell division, cell elongation and distribution of α-, β- and γ-crystallins in the rat lens , 1978 .

[19]  E. Southern Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[20]  U. Schibler,et al.  Changes in size and secondary structure of the ribosomal transcription unit during vertebrate evolution. , 1975, Journal of molecular biology.

[21]  C. Cepko,et al.  Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. , 1987, Proceedings of the National Academy of Sciences of the United States of America.