Gender stereotypes after thirty years: a replication of Rosenkrantz, et al. (1968).

This study is a partial replication of the 1968 investigation by Rosenkrantz, Vogel, Bee, Broverman, and Broverman of gender stereotypes among college students. Like the students studied 30 years ago, male and female participants in this study showed very high agreement about the typical characteristics of men and women. However, current participants identified significantly fewer gender stereotypes than did those in the earlier study. In contrast to the participants in the original study, current participants judged the traits they associated with women to be significantly more socially desirable, in general, than the traits they associated with men.

The AXB and BXA set of recombinant inbred mouse strains.

The recombinant inbred (RI) set of strains, AXB and BXA, derived from C57BL/6J and A/J, originally constructed and maintained at the University of California/San Diego, have been imported into The Jackson Laboratory and are now in the 29th to 59th generation of brother-sister matings. Genetic quality control testing with 45 proviral and 11 biochemical markers previously typed in this RI set indicated that five strains had been genetically contaminated sometime in the past, so these strains have been discarded. The correct and complete strain distribution patterns for 56 genetic markers are reported for the remaining RI strain set, which consists of 31 living strains and 8 extinct strains for which DNA is available. Two additional strains, AXB 12 and BXA 17, are living and may be added to the set pending further tests of genetic purity. The progenitors of this RI set differ in susceptibility to 27 infectious diseases as well as atherosclerosis, obesity, diabetes, cancer, cleft palate, and hydrocephalus. Thus, the AXB and BXA set of RI strains will be useful in the genetic analysis of several complex diseases.

Lung adenoma structure among inbred strains of mice: the pulmonary adenoma histologic type (Pah) genes.

Urethane-induced, lung adenoma multiplicity and histologic type vary among mouse strains. We asked whether the Pas genes which control multiplicity also determine adenoma structure. Lung adenomas from inbred mice, F1 hybrids, and recombinant inbred mice were classified by growth pattern as either solid or papillary. Since no correlation was observed between adenoma multiplicity and histologic type, no linkage apparently exists between the Pas genes and adenoma morphology. We propose the name Pah (Pulmonary Adenoma Histologic type) for the genes controlling lung adenoma growth patterns. Genetic analysis indicated dominance of the papillary phenotype, and that two or more Pah genes determine adenoma structure.

Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14.

This study was undertaken to determine the genetic control of host susceptibility to coxsackievirus B3 (CVB3)-induced chronic myocarditis in a mouse model. An autosomal recessive autoimmune myocardial disease (amd) gene (possibly more than one gene), which determined susceptibility to CVB3-induced chronic myocarditis in the A/J and DBA/2J inbred mouse strains, was mapped to a segment of chromosome 14. Data from both the AXB/BXA recombinant inbred (RI) strains and the B10.D2(57N) H-8b congenic mice supported this linkage relationship. Analysis of the AXB/BXA RI strain distribution patterns suggested that amd maps distal to the Np-2, Tcr alpha, and Myhc alpha loci.

Genetic analysis of the distribution of corticosterone-containing cells in mouse adrenal cortex.

Strains A/J and C57BL/6J (B6) differ in susceptibility to many neoplasms and infectious agents, with B6 mice generally being more resistant. Glucocorticoids protect against some of these pathologies. We examined the distribution of adrenocortical corticosterone (CS), the major endogenous glucocorticoid in mice, in these strains, using anti-CS serum. A distinct strain difference was found. B6 adrenals exhibited abundant CS-positive cells in cord-like arrays while A/J adrenals contained fewer, randomly arranged CS-positive cells. To quantify these results, each adrenal cortex was divided into eight sectors and each sector was classified as to phenotype. Ninety-three percent of the sectors of B6 cortices exhibited the cord-like pattern, whereas only 15% of the sectors of A/J cortices exhibited this pattern. These differences are consistent with a hypothesis that A/J mice are relatively deficient in the prophylactic activities of endogenous glucocorticoids. Adrenal glands from (C57BL/6J x A/J)F1 hybrid mice had approximately equal proportions of areas exhibiting each phenotype, indicating codominant alleles for this trait. We propose the name Cor for this gene. Thirty AXB and BXA recombinant inbred (RI) lines of mice derived from A/J and B6 progenitors were examined for CS immunostaining. Twenty-eight of them had either predominantly A/J-like or predominantly B6-like phenotypes. These RI data support either of two hypotheses. Hypothesis 1 emphasizes the nearly complete concordance of the RI lines with progenitor phenotypes and proposes that a single Cor gene regulates the distribution of CS-positive cells. Using this model, the strain distribution among RI lines implies linkage of Cor to a region on chromosome 6, 27-37 cM from the centromere. Hypothesis 2, which gives greater weight to the two RI lines with intermediate numbers of CS-positive cells, postulates an epistatic interaction between two Cor loci.

IL9 maps to mouse chromosome 13 and human chromosome 5.

Mouse and human cDNA clones encoding the T-cell and mast cell growth factor P40, now designated IL-9, were used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between inbred strains of mice and interspecific backcross progeny. Segregation of mouse and human chromosomes among somatic cell hybrids indicated a location on mouse chromosome 13 and human chromosome 5. RFLPs were identified among inbred strains of mice. Analysis of chromosome 13 alleles for Tcrg, Dhfr, and Il-9 in an interspecific cross between Mus musculus and NFS/N or C58/J mice indicates that IL9 is distal to Tcrg and proximal to Dhfr.

The structural genes encoding P450scc and P450arom are closely linked on mouse chromosome 9.

The chromosomal location of the two genes that encode the cytochrome P450 enzymes, P450SCC (cholesterol side-chain cleavage) and P450arom (aromatase), was identified in the mouse. Genomic DNA from several progenitor strains of recombinant inbred (RI) strains of mice was tested with various restriction endonucleases for restriction fragment length variations. Variation in Bam HI fragment length was detected between A/J and C57BL/6J. Genomic DNA from 43 RI strains derived from A/J and C57BL/6J was analyzed in a similar manner. Complete concordance of the strain distribution pattern for P450SCC and that of P450arom was observed for 43 RI strains. The lack of recombination indicates that the structural genes encoding P450SCC and P450arom are closely linked. The strain distribution patterns of the P450SCC and P450arom genes were compared with other markers previously mapped in these RI lines. The results demonstrate that both P450SCC and P450arom are found on mouse chromosome 9. Of the other loci on mouse chromosome 9, P450SCC and P450arom are most closely linked to the gene encoding P1450. Among 31 RI strains for which the three loci were analyzed, only one example of discordance was found. Human P450SCC, P450arom and P1450 have been mapped to human chromosome 15. However, the distance between the human P450SCC gene and other loci has not been determined. The information presented in this report, along with other studies, indicate conservation between homologous human and mouse chromosomal regions and suggest that human P450SCC will be found to be closely linked with human P450arom.

Ath-2, a second gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.

Strain C57BL/6J and A/J differ at two genes determining atherosclerosis susceptibility. The first gene, Ath-1, was described earlier and this report characterizes Ath-2. The alleles at Ath-2 are r for resistance and s for susceptibility to atherosclerosis. The resistant phenotype in female mice is characterized by high plasma high density lipoprotein-cholesterol levels (74 mg/dl +/- SEM 2) and very few lesions/mouse after 14 weeks of consumption of an atherogenic diet (0.1 +/- SEM 0.1 in a predetermined region of the aorta). The susceptible phenotype in female mice is characterized by low levels of high density lipoprotein-cholesterol (35 mg/dl +/- SEM 1) and 1.2 lesions/mouse +/- SEM 0.2 in the same region of the aorta. In Ath-2 heterozygotes, resistance is dominant to susceptibility. Recombinant inbred strains derived from C57BL/6 and A were characterized for Apoa 1, Apoa 2 and susceptibility to atherosclerosis. Ath-1 and Ath-2 interact with each other so that resistant alleles at either locus confer a resistant phenotype to the animal. The map position of Ath-2 is not known, but Ath-2 does not map near genes determining the apolipoproteins for A-I, A-II, or E.

Strain dependent response of circadian rhythms during exposure to continuous illumination.

Enzymes activities were measured, at three hours intervals, during 30 hours, in various tissues of C57BL/6J and A/J male mice. The measurements, were carried out on mice which were exposed for two, five and twenty one days to continuous illumination. Identical measurements were performed also on mice which were kept in alternating 14 hours light: 10 hours dark. Activity patterns of each group were analysed to test the presence, or absence, of rhythm characteristics. The results of the experiments with C57BL/6J have been previously reported. The comparison of the results, which were obtained from the two strains revealed that under exposure to alternating light: dark conditions all activity patterns exhibited a significant circadian rhythm. Except for one enzyme (thymus GAPD), the times of peak activity (acrophase) were identical for all other examined enzymes, in both strains. On the other hand when the two strains were exposed to continuous illumination they differed in their response to the effect of continuous light. The activity of the same enzyme exhibited different periodicity and/or different acrophase in each of the two strains. This variability reflects the existence of genetic differences, between the strains in the free running behavior of these enzymes' activity rhythms.

Linkage of Nat and Es-1 in the mouse and development of strains congenic for N-acetyltransferase.

The human polymorphism in the hepatic enzyme N-acetyltransferase (NAT) affects the rate at which individuals acetylate, and in many cases detoxify, aromatic amine and hydrazine drugs and xenobiotics. Differences in NAT activity are known to affect individual susceptibility to drug toxicities and are thought to play a part in some spontaneous disorders. A mouse model for the human acetylation polymorphism has been previously characterized and involves the A/J (slow acetylator) and C57BL/6J (rapid acetylator) inbred strains. Strain distribution analysis of 40 A x B and B x A recombinant inbred (RI) strains indicated linkage between the N-acetyltransferase gene (Nat) and the esterase 1 (Es-1) gene, located on mouse chromosome 8. A double backcross involving 107 animals confirmed the recombination frequency between Nat and Es-1 to be 12 +/- 3% (mean +/- SE). The information obtained in the backcross and RI studies was combined, yielding a 13 +/- 2.8% (mean +/- SD) recombination frequency. The Es-1 genotype was determined in our newly developed congenic strains A.B6-Natr and B6.A-Nats. The B6.A-Nats strain has the Es-1 genotype of its inbred partner, the B6 strain, and the A.B6-Natr strain has the Es-1 genotype of the donor strain. These congenic strains will be important in determining the role of the NAT genotype in susceptibility to arylamine-induced cancer and other disorders.

Mapping and gene order of U1 small nuclear RNA, endogenous viral env sequence, amylase, and alcohol dehydrogenase-3 on mouse chromosome 3.

Linkage was established between a number of genes that map on chromosome 3 by studying the distribution patterns of DNA polymorphisms and protein electrophoretic mobility polymorphisms in recombinant inbred (RI) strains of mice. This analysis resulted in the following suggested gene order between the newly assigned genes and previously mapped genes: gamma-fibrinogen (Fgg), Xmmv-22 of mink cell focus-inducing (MCF) virus, U1b small nuclear RNA gene cluster (Rnu-1b), amylase (Amy-1,2), cadmium resistance (cdm), alcohol dehydrogenase-3 (Adh-3), alcohol dehydrogenase-1 (Adh-1). In situ hybridization to chromosome spreads confirmed the assignment of the Ulb small nuclear RNA (snRNA) gene cluster and the gamma-fibrinogen gene to the center of chromosome 3.

The embryonic and adult mouse U1 snRNA genes map to different chromosomal loci.

The linkage relationships of mouse adult (mU1a) and embryonic (mU1b) U1 snRNA genes were determined by analysis of the strain distribution patterns of two polymorphic variant RNAs, mU1a2 and mU1b3, in several recombinant inbred strain systems. The locus for mU1b3 RNA maps to the U1 gene cluster, Rnu1b, located near the center of chromosome 3, whereas the locus for mU1a2 RNA, Rnu1a2, is located in the proximal region of chromosome 12, tightly linked to D12-1. Moreover, the lack of linkage between Rnu1a2 and the locus for mU1a1 genes on chromosome 11 demonstrates that the mouse genome contains at least three clusters of U1 snRNA genes.

KRAS2 as a genetic marker for lung tumor susceptibility in inbred mice.

An Eco-RI restriction fragment length polymorphism occurring in a DNA fragment containing the first exon of the murine KRAS2 gene was shown to correlate with the inherited susceptibility of inbred strains of mice to urethan (CAS: 51-79-6)-induced pulmonary adenomas. Eco-RI digestion of murine DNA yielded four KRAS2-specific fragments. Polymorphic variation occurred in the smallest molecular-weight fragment with alleles of either 0.70 or 0.55 kb in size. Genotyping of 14 inbred strains of mice revealed a correlation between KRAS2 Eco-RI polymorphic variation and the differential susceptibility among inbred strains to development of pulmonary adenomas. Strains with a high incidence of pulmonary adenomas, either spontaneously occurring or in response to carcinogen induction, had the 0.55-kb KRAS2 allele whereas adenoma-resistant strains had the 0.70-kb allele. Analysis of a series of recombinant inbred strains (AXB, BXA) that developed from reciprocal crosses between a highly susceptible strain (A/J) and a highly resistant strain (C57BL/6J) revealed a statistically significant threefold difference in lung tumor susceptibility on the basis of KRAS2 genotype. Further analysis of individual F2 mice of a C57BL/6 female X A/J male cross also demonstrated a threefold difference in tumor susceptibility on the basis of KRAS2 allelic variation.

Genetic regulation of lipopolysaccharide-induced interleukin 1 production by murine peritoneal macrophages.

The production of IL 1 by LPS-stimulated peritoneal macrophages from inbred mouse strains was studied. Macrophages from A/J (A) mice were deficient in IL 1 production, when compared with high IL 1-producing strains, including C57BL/6J (B). The difference between A and B macrophages was maintained over a wide LPS concentration range and throughout a 72-hr incubation period. Because of these differences, it was possible to investigate the mechanisms regulating IL 1 production by applying techniques of genetic analysis by using recombinant inbred (RI) strains derived from the A and B progenitors. A strain distribution pattern (SDP) of IL 1 production (low/high response) was obtained with the use of 15 AXB/BXA RI strains. This suggested the presence of a major gene locus controlling the production of IL 1 in response to LPS stimulation, with allelic differences presumably resulting in deficient or efficient IL 1 production. In addition, there appeared to be one or more other loci involved in determining the magnitude of the IL 1 response to LPS in the responder mice. The IL 1 response did not appear to be linked to the major histocompatibility complex, since B10.A mice (which share the same H-2a haplotype as A/J) were efficient IL 1 producers. There did not appear to be any correlation between the degree of IL 1 production and the magnitude of the peritoneal macrophage inflammatory response, or between IL 1 production and LPS responsiveness (as determined by splenocyte proliferation). SDP analysis also indicated that the IL 1 response was not linked to macrophage tumoricidal activity. A comparison of the SDP for IL 1 production with a library of SDP for other known genetic waits suggested linkage with at least four loci on chromosome 1.

Murine Ly-6 multigene family is located on chromosome 15.

Murine Ly-6-encoded molecules play an important role in the antigen-independent activation of lymphocytes. We have described the cloning of a cDNA encoding the protein component of an Ly-6 molecule. Hybridization studies indicated that this cDNA identified multiple DNA fragments on Southern blots. The banding pattern exhibits a restriction fragment length polymorphism from mice bearing either the Ly-6a or the Ly-6b allele. We have employed three independent chromosomal mapping techniques, somatic cell hybrids, in situ hybridization, and strain distribution pattern analysis of the restriction fragment length polymorphism of DNA from recombinant inbred lines, to ascertain the chromosomal origins of these bands. We report that all members of the Ly-6 multigene family are tightly linked on chromosome 15 and have been regionalized by in situ hybridization analysis to band 15E on the distal portion of this chromosome. Linkage analysis has indicated that the Ly-6 genes are located within 1 map unit of Env-54 (a retroviral envelope restriction fragment length polymorphism probe), 3 map units from ins-1, (insulin-related gene), and 4 map units from the protooncogene c-sis. The possible involvement of the Ly-6 lymphocyte activation and differentiation antigen genes in chromosome 15-related lymphoid malignancies is discussed.

Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1 --Gdc-1 region to mouse chromosome 15.

Previous work has demonstrated linkage between Ly-6, H-30, and a locus, Ril-1, that affects susceptibility to radiation-induced leukemia. Results or preliminary linkage analyses suggested further that the cluster might be linked to Ly-11 on the proximal portion of mouse chromosome 2. Using molecular probes to examine somatic cell lines and recombinant inbred and congenic strains of mice, we have re-evaluated these linkage relationships. A cloned genomic DNA fragment derived from a retroviral site has been used to define a novel locus, Pol-5, that is tightly linked to both H-30 and Ril-1 as shown by analysis of the B6.C-H-30c congenic mouse strain. Following the segregation of the Pol-5 mouse-specific DNA fragment in a series of somatic cell hybrids carrying various combinations of mouse chromosomes on a rat or Chinese hamster background mapped Pol-5 to mouse chromosome 15. During the course of these studies, restriction fragment length polymorphisms were defined associated with several loci, including Pol-5, Ly-6, Sis, Ins-3, Krt-1, Int-1, and Gdc-1. Three of these loci, Sis, Int-1, and Gdc-1, have been previously mapped to chromosome 15 by others using somatic cell hybrids or isoenzyme analyses. Following the inheritance of these eight loci in recombinant inbred strains of mice allowed the definition of a linkage group on the chromosome with the order Ly-6--Ril-1--Sis--H-30--Pol-5--Ins-3--Krt-1--Int-1--Gdc-1. Analyses of alleles inherited as passengers in B6.C-H-30c, C3H.B-Ly-6b, and C57BL/6By-Eh/+ congenic mouse strains and in situ hybridization experiments support the above gene order and indicate further that the cluster is located on distal chromosome 15, with Ly-6 and Sis near Eh.

Circadian rhythms of enzymes' activity in mice tissues during exposure to continuous illumination.

Activity rhythms of enzymes were determined in various tissues of C57BL/6J male mice. The determinations were carried out on mice which were kept in 14 hr light: 10 hr dark regimen, and on day 2, day 5 and day 21 during exposure to continuous illumination. Locomotor activity rhythms were followed in light: dark and up to the seventh day in constant light. All the activities exhibited a significant circadian rhythm in the light: dark regimen. During the exposure to continuous illumination, the locomotor activity exhibit a free running circadian rhythm with a consistent 24 hr and 40 min, major period component. At the same time recording the rhythms of enzyme activity; enzymes exhibited various formats of response which differed from those of the locomotor activity. The results suggest that rhythms of enzyme activity, as well as the desynchronization of the rhythms, are not enzyme specific.

Susceptibility to urethan-induced pulmonary adenomas between A/J and C57BL/6J mice: use of AXB and BXA recombinant inbred lines indicating a three-locus genetic model.

For insight into the number of genes governing differential susceptibility such as in mice of the inbred strain A/J (A) highly susceptible to the induction of pulmonary adenomas by urethan in comparison to resistant strain C57BL/6J (B6) mice, tumor induction was studied in the AXB and BXA series of recombinant inbred (RI) strains derived respectively from A female X B6 male and B6 female X A male ancestral lines. Mice from 46 of these lines were given injections with 1 mg urethan/g (body wt), and the tumor number was assessed 4 months later. Lung tumor multiplicity for several RI lines was independently characterized in the Boulder, CO, and Montreal laboratories, and very similar numbers were obtained. Most lines had multiplicities intermediate to those of the progenitor strains, clearly indicating that more than a single gene accounted for the differences in lung tumor susceptibility between A and B6. The tumor incidence and multiplicity data fit very closely to what would be expected under a three-locus model, and we designated these genes "Pas" for pulmonary adenoma susceptibility. One locus called "Pas-1" had an effect on tumor multiplicity greater than that of the other loci.