Genetic evidence for two t complex tail interaction (tct) loci in t haplotypes.

The t complex on chromosome 17 of the house mouse is an exceptional model for studying the genetic control of transmission ratio, gametogenesis, and embryogenesis. Partial haplotypes derived through rare recombination between a t haplotype and its wild-type homolog have been essential in the genetic analysis of these various properties of the t complex. A new partial t haplotype, which was derived from the complete tw71 haplotype and which is called tw71Jr1, was shown to have unexpected effects on tail length and unique recombination breakpoints.

The murine retinoblastoma homolog maps to chromosome 14 near Es-10.

Restriction fragment length variants have been exploited to map genetically Rb-1, the murine homolog of the human retinoblastoma gene. Rb-1 localized to mouse chromosome 14 on the basis of results from analysis of somatic cell hybrids. In an interspecific backcross involving Mus spretus, Rb-1 and the murine homolog of the human esterase D gene (ESD), which we refer to here as Esd, were inseparable.

The cardiac actin locus (Actc-1) is not on mouse chromosome 17 but is linked to beta 2-microglobulin on chromosome 2.

A restriction fragment variant and recombinant inbred strains were used to show that the cardiac actin locus (Actc-1) is closely linked to beta 2-microglobulin (B2m) and several other loci on chromosome 2 of the mouse. Close linkage of Actc-1 and B2m in both man and mouse provides another example of a chromosomal segment that has been conserved since the divergence of the lineages leading to these two species.

Structural basis for DNA bending.

We report proton NMR studies on DNA oligonucleotides that contain A tracts of lengths known to produce various degrees of bending. Spectra of duplexes in the series 5'-(GGCAnCGG).(CCGTnGCC) (n = 3, 4, 5, 7, 9) reveal substantial structural changes within the An.

Synteny on mouse chromosome 5 of homologs for human DNA loci linked to the Huntington disease gene.

Comparative mapping in man and mouse has revealed frequent conservation of chromosomal segments, offering a potential approach to human disease genes via their murine homologs. Using DNA markers near the Huntington disease gene on the short arm of chromosome 4, we defined a conserved linkage group on mouse chromosome 5. Linkage analyses using recombinant inbred strains, a standard outcross, and an interspecific backcross were used to assign homologs for five human loci, D4S43, D4S62, QDPR, D4S76, and D4S80, to chromosome 5 and to determine their relationships with previously mapped markers for this autosome.

Maps of linkage and synteny homologies between mouse and man.

The recent introduction of biochemical and molecular methods for characterizing and mapping genes has dramatically increased the number of homologous genes that have been mapped in more than one species. This review assesses the status of the map of genes whose chromosomal locations have been determined in both mouse and man, evaluates progress towards saturated maps, and illustrates the manner in which this information is now being used in fields as diverse as medical and evolutionary genetics.

Genic differentiation and origin of Robertsonian populations of the house mouse (Mus musculus domesticus Rutty).

This paper examines the relation between chromosomal and nuclear-gene divergence in 28 wild populations of the house mouse semi-species, Mus musculus domesticus, in Western Europe and North Africa. Besides describing the karyotypes of 15 of these populations and comparing them to those of 13 populations for which such information was already known, it reports the results of an electrophoretic survey of proteins encoded by 34 nuclear loci in all 28 populations. Karyotypic variation in this taxon involves only centric (or Robertsonian) fusions which often differ in arm combination and number between chromosomal races.

Alpha-adrenergic blockade makes minimal contribution to ketanserin's hypotensive effect.

Ketanserin is a selective (S2) serotonin receptor antagonist currently under investigation as an antihypertensive. It has been suggested that the antihypertensive action of ketanserin might be principally due to alpha-adrenergic receptor antagonism rather than its effect on serotonin receptors. We therefore determined the contribution of alpha-adrenergic blockade to the hypotensive effects of ketanserin in six patients with hypertension and compared that with the alpha-adrenergic blockade produced by prazosin, a known alpha 1-adrenergic antagonist.

Gene for ovarian granulosa cell tumor susceptibility, Gct, in SWXJ recombinant inbred strains of mice revealed by dehydroepiandrosterone.

Spontaneous, malignant ovarian granulosa cell (GC) tumors occur in pubertal SWR and specific SWXJ recombinant inbred strains of mice. Treatment of these mice with dehydroepiandrosterone (DHEA), an adrenal secretory steroid with anticancer actions against spontaneous and carcinogen-induced tumors of different tissues, gave unexpected results. Diet supplemented with 0.

Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17.

Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid beta precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, we have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers.

Effect of high-dose inhaled budesonide on calcium and phosphate metabolism and the risk of osteoporosis.

We investigated the effects of the antiasthmatic inhaled steroid budesonide at low and high dosage (0.6 and 2.4 mg/day) on calcium and phosphate metabolism (Ca, P) in 10 normal adults.

Electrophysiologic and hemodynamic effects of chronic oral therapy with the alpha 2-agonists clonidine and tiamenidine in hypertensive volunteers.

Clonidine can produce symptomatic sinus bradycardia or atrioventricular (AV) block in some patients. Electrophysiologic studies have been performed after intravenous clonidine in patients showing such side effects; these have demonstrated variable depression of sinus and AV nodal function. We have evaluated the electrophysiologic and hemodynamic effects of chronic oral treatment with either clonidine (0.

Genetic analysis and developmental regulation of testis-specific RNA expression of Mos, Abl, actin and Hox-1.4.

The pattern of Mos proto-oncogene RNA expression in the gonads of the sterile mouse mutants, dominant spotting (W), sex reversal (Sxr), testicular feminization (Tfm), hypogonadal (hpg), quaking (qk), two t-haplotypes, three X-autosomal translocations, and the YPOS strain, is consistent with its presence in haploid spermatids in the testes and in oocytes in the ovaries. In the male-sterile mouse mutants the pattern of expression of the testis-specific transcripts for Abl, actin, and the mouse homeobox Hox-1.4 genes is identical to that observed for Mos.

H-2 polymorphisms are more uniformly distributed than allozyme polymorphisms in natural populations of house mice.

Patterns of H-2 and allozyme polymorphism in natural populations of house mice from Europe, North Africa and South America were analyzed. The purpose of the analysis was to determine whether H-2 and allozyme polymorphisms were similarly distributed both geographically and temporally in wild mice. Two subspecies of house mice, Mus musculus domesticus and M.

The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice.

Polymorphism and linkage of the alpha A-crystallin gene in t-haplotypes of the mouse.

Restriction fragment polymorphisms were used to order the alpha A-crystallin locus (Crya-1) relative to other genes in mouse t-chromatin and to investigate the relatedness of alpha-A-crystallin sequences among different t-haplotypes. Analysis of DNA from t-recombinant mice mapped Crya-1 to the K end of the H-2 complex and within the distal inverted region characteristic of t-haplotypes. Hybridization with Crya-1 cDNA revealed three distinct phenotypic groups among the 17 different t-haplotypes studied.

Rearrangement of genes located on homologous chromosomal segments in mouse and man: the location of genes for alpha- and beta-interferon, alpha-1 acid glycoprotein-1 and -2, and aminolevulinate dehydratase on mouse chromosome 4.

Gene mapping studies to determine the order of alpha- and beta-interferon (Ifa, Ifb), aminolevulinate dehydratase (Lv), and alpha-1 acid glycoprotein-1 and -2 (Orm-1, Orm-2) relative to each other and to the reference genes brown (b), B-cell maturation factor responsiveness (Bmfr-1), and major urinary protein-1 (Mup-1) are reported. The most likely order was Mup-1--Lv--b--Orm-1, Orm-2--Ifa, Ifb--Bmfr-1. This order suggested that two chromosomal segments located on chromosome 4 in the mouse and chromosome 9 in man have been conserved since divergence of lineages leading to man and mouse; these segments are marked by soluble aconitase-1 (Aco-1) and galactose-1 phosphate uridyl transferase (Galt) and by Lv and Orm-1.

A glyoxalase-1 variant associated with the t-complex in house mice.

A quantitative variant of glyoxalase-1 associated with the t-complex in house mice is described. GLO-1C in red cell lysates from mice heterozygous for complementing t-haplotypes and from mice homozygous for the tw8-haplotype had less than one-third the GLO-1 activity of NZB/BlNJ, the inbred strain with the lowest activity previously reported. GLO-1C appeared to be determined by the structural locus Glo-1 and, together with two partial t6-haplotypes, was used to map Glo-1 to the telomeric portion of the t6-haplotype.

Plasma catecholamine modulation of alpha 2 adrenoreceptor agonist affinity and sensitivity in normotensive and hypertensive human platelets.

We measured alpha 2-adrenoreceptor density as well as affinity for and sensitivity to agonist on intact platelets of normotensive and hypertensive subjects before and after physiological increases in plasma catecholamines. In normotensives, posture-induced rises in plasma catecholamines correlated with reduced alpha 2-adrenoreceptor agonist affinity and fewer high affinity state receptors. Platelet aggregation and inhibition of adenylate cyclase by L-epinephrine also was reduced.

Two loci affecting B cell responses to B cell maturation factors.

B lymphocytes from DBA/2Ha mice have a genetic defect characterized by a failure to differentiate into antibody-secreting cells in response to a family of lymphokines termed B cell maturation factors (BMFs). By contrast, B cells from DBA/2Ha mice respond normally in PFC assays to the B cell mitogen LPS, and macrophages from these mice are activated by one of the three BMFs. Two loci are responsible for the B cell defect in DBA/2Ha mice.