Mapping of 19032 mouse cDNAs on mouse chromosomes

Finding genes by the positional candidate approach requires abundant cDNAs mapped to chromosomes. To provide such important information, we computationally mapped 19032 of our mouse cDNAs to mouse chromosomes by using data from public databases. We used 2 approaches. In the first, we integrated the mapping data of cDNAs on the human genome, known gene-related data, and comparative mapping data. From this, we calculated map positions on the mouse chromosomes. For this first approach, we developed a simple and powerful criterion to choose the correct map position from candidate positions in sequence homology searches. In the second approach, we related cDNAs to expressed sequence tags (EST) previously mapped in radiation hybrid experiments. We discuss improving the mapping by combining the 2 methods.     

Supermelanotic hybrids between mouse teratocarcinoma and mouse melanoma cells

Each of four kinds of teratocarcinoma cells, OTT6050P, PCC4, PSA1 and LT, derived from 129 or LT mouse strain, was fused with B16-CAPr melanoma cells derived from C57BL/6J by using Sendai virus. The resultant hybrids were morphologically melanotic melanoma cells which were larger and more heavily pigmented than the parental B16-CAPr melanoma cells. The chromosome analysis and GPI electrophoresis demonstrated that all hybrids were products of fusion between a single teratocarcinoma cell and a single melanoma cell. The pigmentation in the hybrids between a 129 teratocarcinoma cell and a melanoma cell was much stronger than that in hybrids between an LT teratocarcinoma cell and a melanoma cell. This phenomenon was consistent with the difference of coat color between 129 and LT mouse strain. From these results, it was suggested that the genes of teratocarcinoma cells involved in the pigmentation are activated in the hybrids with B16-CAPr melanoma cells.     

Pathogenicity of mouse hepatitis virus for preimplantation mouse embryos

Mouse embryos which were hatched from the zona pellucida in vitro in the presence of mouse hepatitis virus (MHV) or outgrown on coverslips and then exposed to MHV were shown by immunohistochemical staining to have virally infected trophoblast cells. Zona-intact embryos incubated with MHV for 48 h (2-cell embryos) or 1.5 h (blastocysts) were resistant to infection. Morulae and early blastocysts collected from donor mice experimentally infected with MHV were not infected, but the medium in which they were flushed from the uterine horns was contaminated with virus. No virus was detected after embryos were washed through three changes of uncontaminated medium. MHV was transmitted to foster mothers when embryos were transferred in medium contaminated with the virus. Fetal and decidual tissues were not infected. We suggest that embryo transfer is an effective and simple alternative to Caesarian rederivation of MHV-contaminated mice.     

The relationship of mouse spermatozoal to mouse testicular cathepsins

Mouse testicular and sperm-associated cathepsin activities were compared for optimal conditions of assay, molecular sieving properties, inhibition data, and electrophoretic mobility. An extract of testes had several isoenzymes of cathepsin among which cathepsin B1 may be a major form while a sperm-associated component may be a minor form. The sperm-associated component was highly sensitive to pepstatin and may be cathepsin D.     

Cryopreservation of mouse spermatozoa: double your mouse space

Cryopreservation of mouse germplasm is an important tool to secure, archive and distribute mouse lines of different origin. While embryo freezing has been standard procedure for many years, major advantages in freezing spermatozoa have been made recently that open new opportunities for management of mouse colonies.     

Centralized mouse repositories

Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.     

Human mouse trap

A new biometric that tracks the unique movements created when a user signs their name using a regular computer mouse could be an excellent and cheap addition to improve computer security. Although at an early stage of development, the technology has already received significant interest and with further work could be a commercially viable product.     

Frataxin knockin mouse

Friedreich ataxia is the consequence of frataxin deficiency, most often caused by a GAA repeat expansion in intron 1 of the corresponding gene. Frataxin is a mitochondrial protein involved in iron homeostasis. As an attempt to generate a mouse model of the disease, we introduced a (GAA)(230) repeat within the mouse frataxin gene by homologous recombination. GAA repeat knockin mice were crossed with frataxin knockout mice to obtain double heterozygous mice expressing 25-36% of wild-type frataxin levels. These mice were viable and did not develop anomalies of motor coordination, iron metabolism or response to iron loading. Repeats were meiotically and mitotically stable.     

Cat and mouse

The role of cathepsin B, a lysosomal protease implicated in amyloid-beta (Abeta1-42) metabolism, in Alzheimer's disease remains controversial. In this issue of Neuron, Mueller-Steiner et al. manipulate the expression of cathepsin B in aged APP transgenic mice, observing that increased expression degrades preformed oligomeric and fibrillar amyloid, while inactivation accelerates beta-amyloidosis.     

A new mouse model for infantile neuroaxonal dystrophy,inad mouse, maps to mouse Chromosome 1

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive hereditary neurodegenerative disease of humans. So far, no responsible gene has been cloned or mapped to any chromosome. For chromosome mapping and positional cloning of the responsible gene, establishment of an animal model would be useful. Here we describe a new mouse model for INAD, named inad mouse. In this mouse, the phenotype is inherited in an autosomal recessive manner, symptoms occur in the infantile period, and the mouse dies before sexual maturity. Axonal dystrophic change appearing as spheroid bodies in central and peripheral nervous system was observed. These features more closely resembled human INAD than did those of the gad mouse, the traditional mouse model for INAD. Linkage analysis linked the inad gene to mouse Chromosome 1, with the highest LOD score (=128.6) at the D1Mit45 marker, and haplotype study localized the inad gene to a 7.5-Mb region between D1Mit84 and D1Mit25. In this linkage area some 60 genes exist: Mutation of one of these 60 genes is likely responsible for the inad mouse phenotype. Our preliminary mutation analysis in 15 genes examining the nucleotide sequence of exons of these genes did not find any sequence difference between inad mouse and C57BL/6 mouse.     

Replication of mouse cytomegalovirus in thymidine kinase-deficient mouse cells.

In an attempt to determine whether mouse cytomegalovirus (MCMV) requires thymidine kinase (TK) for replication and whether it induces TK, TK-deficient mouse cells were isolated and used as host cells for MCMV. Mutant cells resistant to 200 μg/ml of 5-Bromodeoxyuridine (BUdR) were selected from SV40-transformed mouse cells, mks-A TU-7, by propagating the cells in the presence of varying concentrations of BUdR graded by serial 2-fold increments. The mutant cells, designated as TU-7 BU, showed a very low TK activity (less than 1/20 that of mks-A TU-7). Herpes simplex virus type 1 (HSV-1) replicated in starved as well as in unstarved TU-7 BU, whereas MCMV could replicate only in growing TU-7 BU and could not form plaques in monolayers of mks-A TU-7 or TU-7 BU. HSV-1 infection enhanced TK activity equally in both mks-A TU-7 and TU-7 BU. In contrast, TK activity of MCMV-infected mks-A TU-7 was lower than that of uninfected cells or cells inoculated with UV-inactivated virus. In addition, TK activity of the MCMV-infected TU-7 BU remained minimal without showing any increase. The replication of HSV-1 was completely inhibited in the presence of BUdR (10 μg/ml), whereas MCMV could replicate even in the presence of 50 μg/ml of BUdR. The results indicate that MCMV neither requires TK nor induces TK activity in the infected cells.     

Supermelanotic hybrids derived from mouse melanomas and normal mouse cells

Hybrids formed between HPRT- Cloudman mouse melanoma and normal cells were isolated. The parental origin of the hybrids was verified by isoenzyme and karyotype analyses. These hybrid cells differed in two major characteristics from hybrids of melanoma and established fibroblastic cells. (1) They grew as tumors when injected into mice, and (2) they expressed differentiated melanocytic functions. At least one of the differentiated functions was overexpressed. The specific activity of tyrosinase was 3-20 times higher in the hybrid cells than in the parental mouse melanoma. The overexpression of tyrosinase in these hybrid cells has been stable for more than a year, has been transmitted to subclones of the original hybrid cell lines, and has been expressed in tumors that grew after injections of hybrid cells into animals.     

Behavioral effect of mouse fibrinopeptide A on mouse forced swimming

A specific dopamine 2 receptor antagonist, (-)sulpiride, induced an anti-depressive behavior, climbing, in mice forced to swim for 6 h after the injection. The effective fraction was divided from the mouse serum using an ion exchanger and an ultra filtration method. This fraction contained fibrinopeptide A. A peptide synthesized according to the primary 6-amino acid sequence (TDTEDK) of fibrinopeptide A also remarkably increased the behavior. The present findings clearly indicate that a peptide with TDTEDK showed anti-depressive activity.     

Know thy mouse

In science it is imperative that the basic reagents and materials are defined and uniform. Unlike chemical reagents, which are uniform over time, mice, like all living creatures, have an intrinsic genetic drive to change, with mutations accumulating over time leading to increasing genetic variation and phenotypic change. Such changes compromise the reproducibility of experimental data over time and place. The use of the mouse has expanded rapidly in recent years and many scientists who have turned to the mouse as a research model might be unaware of the profound impact of changes in genetic background. Here we discuss the sources of genetic change and strategies to reduce them with the idea of strengthening international genetic standards for inbred mice.