The Mcs7 quantitative trait locus is associated with an increased susceptibility to mammary cancer in congenic rats and an allele-specific imbalance.

Identification of high-penetrance breast cancer genes such as Brca1 has been accomplished by analysing familial cases. However, these genes occur at low frequency and do not account for the majority of genetic risk. Identification of low-penetrance alleles that occur commonly in populations may benefit from unbiased genome-wide screening.

Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer.

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background.

Production of knockout rats using ENU mutagenesis and a yeast-based screening assay.

The rat is a widely used model in biomedical research and is often the preferred rodent model in many areas of physiological and pathobiological research. Although many genetic tools are available for the rat, methods to produce gene-disrupted knockout rats are greatly needed. In this study, we developed protocols for creating N-ethyl-N-nitrosourea (ENU)-induced germline mutations in several rat strains.

Genetic loci controlling breast cancer susceptibility in the Wistar-Kyoto rat.

In this study, the Wistar-Kyoto (WKy) rat was genetically characterized for loci that modify susceptibility to mammary carcinogenesis. We used a genetic backcross between resistant WKy and susceptible Wistar-Furth (WF) rats as a panel for linkage mapping to genetically identify mammary carcinoma susceptibility (Mcs) loci underlying the resistance of the WKy rat. Rats were phenotyped for DMBA-induced mammary carcinomas and genotyped using microsatellite markers.

Genetic mapping of the rat Lcn2 gene to chromosome 3.

The expression of rat 24p3, encoded by the Lcn2 gene, has been associated with rat mammary carcinomas initiated by the neu oncogene (Stoesz and Gould, 1995). In this study, we assign the Lcn2 gene to rat chromosome band 3q12 by genetic linkage analysis.

Linkage mapping of rat chromosome 5 markers generated from chromosome-specific libraries.

Seventy-six novel microsatellite markers with various simple sequence repeat (SSR) motifs are reported in this paper. They were generated on the basis of non-radioactive library screening procedures from flow-sorted rat Chromosome (Chr) 5-specific DNA, and were mapped in three rat backcross populations. Fifty-four of these markers mapped to Chr 5, while the other 22 mapped to other chromosomes of the rat genome.

The genetic components of susceptibility to breast cancer in the rat.

The rat is an extremely valuable model for studies of inherited susceptibility to breast cancer because the characteristics of rat mammary cancer and human breast cancer are so similar. There are now several rat models for studying sensitivity versus resistance, or cell autonomy versus non-cell-autonomy, for spontaneous and induced mammary cancers. It is known that the tumor-resistant Cop [20, 21] and WKy [8] strains carry dominant resistance genes that inhibit both spontaneous and induced mammary tumors.

A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors.

In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given either N-nitroso-N-methylurea (NMU) or N-butyl-(hydroxybutyl)-nitrosoamine (BBN), and mammary and bladder tumors were collected at 15 and 52 wk after treatment, respectively.

Mapping of 55 new rat microsatellite markers from chromosome-specific libraries.

Fifty-five novel rat microsatellite markers were isolated from libraries specific for rat chromosomes (Chrs) 1, 2, and 7. The markers were mapped in three backcross rat populations. Thirty of these markers mapped to Chrs 1, 2, or 7, while the other 25 mapped to other chromosomes.

Genetic identification of multiple loci that control breast cancer susceptibility in the rat.

We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3.

Genetic linkage mapping of 11 novel DNA markers and the ceruloplasmin (Cp) gene on rat chromosome 2.

We have mapped 11 novel, anonymous genetic markers to rat chromosome 2. The rat ceruloplasmin gene (Cp) had been previously mapped to chromosomes 2 and 7q11-->q13 by two different methods. To resolve the assignment and to localize the Cp gene on the rat genetic linkage map, we used linkage analysis to confirm that rat Cp lies on chromosome 2.

Cloning, genetic mapping and expression studies of the rat Brca1 gene.

The breast cancer gene BRCA1 has previously been cloned from both human and mouse. We cloned a fragment of the rat Brca1 homologue in order to map it and explore its biological function. Partial cDNA fragments of the rat Brca1 homologue were isolated by RT-PCR.

Genetic identification of Mcs-1, a rat mammary carcinoma suppressor gene.

Women have inherited differences in their susceptibility to breast cancer, but the genes underlying this variation are difficult to identify. We have approached the problem of identifying breast cancer susceptibility genes by using a rat model. Inbred rat strains display differential susceptibilities to mammary carcinogenesis; the Copenhagen (COP) rat is resistant, while the Wistar-Furth (WF) rat is susceptible to induction of mammary tumors by 7,12-dimethylbenz[a]anthracene.

Bivariate flow karyotyping, sorting, and peak assignment of all rat chromosomes.

A bivariate flow cytometric rat karyotype was established from second- and third-passage Copenhagen (Cop) rat embryo cell cultures. Chromosome suspensions from such cells (2n = 42 chromosomes) yielded bivariate flow karyotypes composed of 14-18 peaks, 10 of which were sortable into pools of single chromosome types. Conditions affecting resolution of peaks (including the length of colcemid treatment of cells and various combinations of fluorescent and nonfluorescent dyes) were optimized.

Transplacental transmission of a leukemogenic murine leukemia virus.

Recombinant inbred BXH-2 mice spontaneously produce a B-tropic murine leukemia virus (MuLV) beginning early in life and have a high incidence of spontaneous myeloid leukemia. These traits are not characteristic of the progenitor strains (C57BL/6J and C3H/HeJ) or of 11 other recombinant inbred BXH strains. Genetic analysis has shown that the virus is not transmitted through the germ line, suggesting that the virus is passed from one generation to the next by horizontal transmission.

Relationship of polymorphisms near the rat prolactin, N-ras, and retinoblastoma genes with susceptibility to estrogen-induced pituitary tumors.

Chronic treatment of rats with the synthetic estrogen diethylstilbestrol is known to induce the formation of pituitary tumors, and such tumor induction is highly dependent on the strain of rat used. We examined three previously discovered restriction fragment length polymorphisms in rats to determine whether these correlated with susceptibility to tumor formation. The results indicate that the presence of particular alleles of the polymorphic N-ras and retinoblastoma (Rb) genes does not correlate with tumor susceptibility.

Restriction fragment length polymorphisms in the rat N-ras and retinoblastoma genes: their identification and characterization.

We have observed restriction fragment length polymorphisms for the N-ras and retinoblastoma (Rb) genes between rat strains that are susceptible or resistant to induction of pituitary tumors by diethylstilbestrol (DES). Thirteen other proto-oncogenes tested displayed the same restriction patterns between all samples. The N-ras polymorphism is observed with more than one restriction nuclease and the N-ras and Rb polymorphisms are not a result of DES treatment.

Toward the development of self-help health behaviour change programs: weight loss by correspondence.

The goal of this study was to evaluate a correspondence weight control program, and to assess the impact of three program elements (weekly homework, interim weigh-ins, and participation deposits) individually and in combination. All treated participants received 15 weekly standard lessons by mail. Three program features were varied factorially: a) homework assignments, b) interim weigh-ins and c) a deposit refunded contingent on returning homework and/or attending interim weigh-ins.

Effects of breast cancer and mastectomy on emotional support and adjustment.

Wortman and Dunkel-Schetter (J. Soc. Issues 35, 120-155, 1979) have argued that victims of misfortune are likely to experience reduced social support at a time when support is needed most.

Steroid hormone receptors and oncogenes.

Steroid hormones exert diverse effects on normal growth and development through the action of specific intracellular receptor molecules. These receptors are thought to function as trans-acting regulatory proteins by interacting with chromatin and modulating the transcription of specific genes in target cells. Another class of molecules, the viral oncogenes (v-oncs) encode proteins which are associated with the transformation of normal cells to cancer cells.

Fragile (X) X-linked mental retardation I: relationship between age and intelligence and the frequency of expression of fragil (X)(q28).

Members of eight Saskatchewan families with fragile (X) X-linked mental retardation were studied in an attempt to relate frequency to age and intelligence. The mean IQ of 37 affected men was 35 (range 10-66). The mean IQ of 32 carriers was 88 (range 57-119), and the mean IQ of 13 females who remain at risk for being carriers, have no affected sons, and who failed to demonstrate the fra(X) was 100 (range 78-126).

Physical and psychological complications after intestinal bypass for obesity.

Cognitive changes, depression, arthralgia and dermatitis developed in a 33-year-old woman 5 years after a jejunoileal shunt for massive obesity, The dermatitis and low serum carotene and vitamin C values suggested vitamin deficiencies, The serum magnesium concentration also was low. Vitamin and mineral replacement led to amelioration of the physical and psychological symptoms; the improvement has been maintained at 18-month follow-up. The favourable changes were documented with the Wechsler Adult Intelligence Scale, the Minnesota Multiphasic Personality Inventory and test performance ratings.