An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway.

Actin nucleation factors function to organize, shape, and move membrane-bound organelles, yet they remain poorly defined in relation to disease. Galloway-Mowat syndrome (GMS) is an inherited disorder characterized by microcephaly and nephrosis resulting from mutations in the gene. This core clinical phenotype appears frequently in the Amish, where virtually all affected individuals harbor homozygous founder mutations in as well as the closely linked gene, which encodes a nucleation factor.

Four core genotypes mouse model: localization of the Sry transgene and bioassay for testicular hormone levels.

Background: The "four core genotypes" (FCG) mouse model has emerged as a major model testing if sex differences in phenotypes are caused by sex chromosome complement (XX vs. XY) or gonadal hormones or both. The model involves deletion of the testis-determining gene Sry from the Y chromosome and insertion of an Sry transgene onto an autosome.

Retroelement demethylation associated with abnormal placentation in Mus musculus x Mus caroli hybrids.

The proper functioning of the placenta requires specific patterns of methylation and the appropriate regulation of retroelements, some of which have been co-opted by the genome for placental-specific gene expression. Our inquiry was initiated to determine the causes of the placental defects observed in crosses between two species of mouse, Mus musculus and Mus caroli. M.

Recent amplification of the kangaroo endogenous retrovirus, KERV, limited to the centromere.

Mammalian retrotransposons, transposable elements that are processed through an RNA intermediate, are categorized as short interspersed elements (SINEs), long interspersed elements (LINEs), and long terminal repeat (LTR) retroelements, which include endogenous retroviruses. The ability of transposable elements to autonomously amplify led to their initial characterization as selfish or junk DNA; however, it is now known that they may acquire specific cellular functions in a genome and are implicated in host defense mechanisms as well as in genome evolution. Interactions between classes of transposable elements may exert a markedly different and potentially more significant effect on a genome than interactions between members of a single class of transposable elements.

Chromosomes, conflict, and epigenetics: chromosomal speciation revisited.

Since Darwin first noted that the process of speciation was indeed the "mystery of mysteries," scientists have tried to develop testable models for the development of reproductive incompatibilities-the first step in the formation of a new species. Early theorists proposed that chromosome rearrangements were implicated in the process of reproductive isolation; however, the chromosomal speciation model has recently been questioned. In addition, recent data from hybrid model systems indicates that simple epistatic interactions, the Dobzhansky-Muller incompatibilities, are more complex.

Orthotopic transplantation of v-src-expressing glioma cell lines into immunocompetent mice: establishment of a new transplantable in vivo model for malignant glioma.

Object: The aim of this study was to develop and characterize a new orthotopic, syngeneic, transplantable mouse brain tumor model by using the cell lines Tu-9648 and Tu-2449, which were previously isolated from tumors that arose spontaneously in glial fibrillary acidic protein (GFAP)-v-src transgenic mice.

Methods: Striatal implantation of a 1-microl suspension of 5000 to 10,000 cells from either clone into syngeneic B6C3F1 mice resulted in tumors that were histologically identified as malignant gliomas. Prior subcutaneous inoculations with irradiated autologous cells inhibited the otherwise robust development of a microscopically infiltrating malignant glioma.

Molecular characterization and evolution of X and Y-borne ATRX homologues in American marsupials.

In eutherians, the sex-reversing ATRX gene on the X has no homologue on the Y chromosome. However, testis-specific and ubiquitously expressed X-borne genes have been identified in Australian marsupials. We studied nucleotide sequence and chromosomal location of ATRX homologues in two American marsupials, the opossums Didelphis virginiana and Monodelphis domestica.