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Results for “Locus Control Region”

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PubMed1999

Two loci, Tmevp2 and Tmevp3, located on the telomeric region of chromosome 10, control the persistence of Theiler's virus in the central nervous system of mice.

Theiler's virus persistently infects the white matter of the spinal cord in susceptible strains of mice. This infection is associated with inflammation and primary demyelination and is studied as a model of multiple sclerosis. The H-2D gene is the major gene controlling viral persistence. However, the SJL/J strain is more susceptible than predicted by its H-2(s) haplotype. An (SJL/J x B10. S)F1 x B10.S backcross was analyzed, and one quantitative trait locus (QTL) was located in the telomeric region of chromosome 10 close to the Ifng locus. Another one was tentatively mapped to the telomeric region of chromosome 18, close to the Mbp locus. We now report the study of 14 congenic lines that carry different segments of these two chromosomes. Although the presence of a QTL on chromosome 18 was not confirmed, two loci controlling viral persistence were identified on chromosome 10 and named Tmevp2 and Tmevp3. Furthermore, the Ifng gene was excluded from the regions containing Tmevp2 and Tmevp3. Analysis of the mode of inheritance of Tmevp2 and Tmevp3 identified an effect of sex, with males being more infected than females.

Analysis of Variance↗
PubMed2006

Chromosome 2 locus Nidd5 has a potent effect on adiposity in the TSOD mouse.

We previously reported a quantitative trait locus for body weight, non-insulin-dependent diabetes 5 (Nidd5), on Chromosome 2 in the TSOD (Tsumura, Suzuki, Obese Diabetes) mouse, a model of polygenic obese type 2 diabetes. To find the gene responsible for a specific component of the pathogenesis, we used a marker-assisted selection protocol to produce congenic strains. These mice are designed to carry a control BALB/cA-derived genomic interval and a TSOD background to look for loss of phenotype. One of the strains with the widest congenic interval, D2Mit297-D2Mit304, showed reductions in both body weight and adiposity compared with TSOD mice. The phenotypic analyses of other congenic strains further narrowed the locus in a 9.4-Mb interval between D2Mit433 and D2Mit91, around which numerous loci for body weight and adiposity have been mapped previously. Although the locus showed a relatively modest effect on body weight, it had a major influence on fat mass that explains approximately 60% of the difference in the adipose index between parental TSOD and BALB/cA mice. Furthermore, the congenic strain with a minimal BALB/cA-derived region showed significantly smaller cell sizes of white and brown adipocytes compared with the control littermates. However, the locus did not primarily affect food consumption, general activity, or rectal temperature after cold exposure, although there are clear differences in these traits between the parental strains. The present work physically delineates the major locus for adiposity in the TSOD mouse.

Adipose Tissue↗
PubMed2005

ZDHHC8 as a candidate gene for schizophrenia: analysis of a putative functional intronic marker in case-control and family-based association studies.

BACKGROUND: The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia. METHODS: Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186). RESULTS: In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity chi2 = 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions. CONCLUSION: The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.

Acyltransferases↗
PubMed2003

Changes in the brain kappa-opioid receptor levels of rats in withdrawal from physical dependence upon butorphanol.

Changes in kappa-opioid receptor levels have been implicated in the development of physical dependence upon and withdrawal from the mixed agonist-antagonist opioid, butorphanol. Immunoblotting analysis was performed to determine the levels of kappa- and mu-opioid receptors in brain regions of rats in withdrawal from dependence upon butorphanol or morphine. Physical dependence was induced by a 72 h i.c.v. infusion with either butorphanol or morphine (26 nmol/microl/h). Withdrawal was subsequently precipitated by i.c.v. challenge with naloxone (48 nmol/5 microl/rat), administered 2 h following cessation of butorphanol or morphine infusion. Immunoblotting analysis of kappa-opioid receptors from butorphanol-withdrawal rats showed significant increases in 11 of 21 brain regions examined, including the nucleus accumbens, amygdala, dorsomedial hypothalamus, hypothalamus, paraventricular thalamus, thalamus, presubiculum, and locus coeruleus, when compared with saline treated, non-dependent controls. In addition, significant reductions were found in the hippocampus and in cortical brain regions, including the parietal cortex and temporal cortex from butorphanol-withdrawal rats. These findings contrasted with those from morphine-withdrawal rats, in which the only changes noted were increases in the thalamus and paraventricular thalamus. Changes in the levels of the mu-opioid receptor protein were observed in 11 of 21 brain regions examined in morphine-withdrawal rats, but only in three of 21 in butorphanol-withdrawal rats. These results implicate a substantive and largely unique role for kappa-opioid receptors in mediation of the development of physical dependence upon, and the expression of withdrawal from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.

Animals↗
PubMed2003

Diabetes protection and restoration of thymocyte apoptosis in NOD Idd6 congenic strains.

Type 1 diabetes in the nonobese diabetic (NOD) mouse is a multifactorial and polygenic disease. The NOD-derived genetic factors that contribute to type 1 diabetes are named Idd (insulin-dependent diabetes) loci. To date, the biological functions of the majority of the Idd loci remain unknown. We have previously reported that resistance of NOD immature thymocytes to depletion by dexamethazone (Dxm) maps to the Idd6 locus. Herein, we refine this phenotype using a time-course experiment of apoptosis induction upon Dxm treatment. We confirm that the Idd6 region controls apoptosis resistance in immature thymocytes. Moreover, we establish reciprocal Idd6 congenic NOD and B6 strains to formally demonstrate that the Idd6 congenic region mediates restoration of the apoptosis resistance phenotype. Analysis of the Idd6 congenic strains indicates that a 3-cM chromosomal region located within the distal part of the Idd6 region controls apoptosis resistance in NOD immature thymocytes. Together, these data support the hypothesis that resistance to Dxm-induced apoptosis in NOD immature thymocytes is controlled by a genetic factor within the region that also contributes to type 1 diabetes pathogenesis. We propose that the diabetogenic effect of the Idd6 locus is exerted at the level of the thymic selection process.

Aging↗
PubMed1993

Mitochondrial DNA sequence analysis of human skeletal remains: identification of remains from the Vietnam War.

Deoxyribonucleic acid (DNA) sequence analysis of the control region of the mitochondrial DNA (mtDNA) genome was used to identify human skeletal remains returned to the United States government by the Vietnamese government in 1984. The postmortem interval was thought to be 24 years at the time of testing, and the remains presumed to be an American service member. DNA typing methods using nuclear genomic DNA, HLA-DQ alpha and the variable number of tandem repeat (VNTR) locus D1S80, were unsuccessful using the polymerase chain reaction (PCR). Amplification of a portion of the mtDNA control region was performed, and the resulting PCR product subjected to DNA sequence analysis. The DNA sequence generated from the skeletal remains was identical to the maternal reference sequence, as well as the sequence generated from two siblings (sisters). The sequence was unique when compared to more than 650 DNA sequences found both in the literature and provided by personal communications. The individual sequence polymorphisms were present in only 23 of the more than 1300 nucleotide positions analyzed. These results support the observation that in cases where conventional DNA typing is unavailable, mtDNA sequencing can be used for human remains identification.

Anthropology, Physical↗
PubMed1999

Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements.

The TGFbeta-related molecule Nodal is required for establishment of the anterior-posterior (A-P) and left-right (L-R) body axes of the vertebrate embryo. In mouse, several discrete sites of nodal activity closely correlate with its highly dynamic expression domains. nodal function in the posterior epiblast promotes primitive streak formation, whereas transient nodal expression in the extraembryonic visceral endoderm is essential for patterning the rostral central nervous system. Asymmetric nodal expression in the developing node and at later stages in left lateral plate mesoderm has been implicated as a key regulator of L-R axis determination. We have analyzed the cis-regulatory elements controlling nodal expression domains during early development. We show that the regulatory sequences conferring node-specific expression are contained in an upstream region of the locus, whereas early expression in the endoderm and epiblast and asymmetric expression at later stages on the left side of the body axis are controlled by a 600-bp intronic enhancer. Targeted deletion of a 100-bp subregion of this intronic enhancer eliminates nodal expression in the early epiblast and visceral endoderm and disrupts asymmetric expression in the node and lateral plate mesoderm. Thus, developmentally regulated nodal expression at distinct tissue sites during A-P and L-R axis formation is potentially controlled by common transcriptional activators.

Animals↗
PubMed1987

Possible association of MN locus haplotypes with essential hypertension.

Five multigenerational kindreds with familial hypertension were typed for human leukocyte antigen (HLA) and blood group antigens to investigate genetic factors that influence variability in blood pressure. Pedigree analysis revealed that children of matings in which both parents were hypertensive had a significantly greater risk of hypertension than children of matings in which one parent or neither parent was hypertensive. Blood types N and MN were abnormally distributed among hypertensive as compared with normotensive members of white but not black families. The distribution of ABO and Rh types was not significantly different between hypertensive and normotensive siblings. When all possible pairings of siblings were examined for HLA haplotype sharing, abnormal distributions were observed among hypertensive sib pairs whereas the expected mendelian segregation was observed among hypertensive-normotensive sib pairs and normotensive-normotensive sib pairs. These results suggest the genetic factors controlling variation in blood pressure may include loci in the region of the MN locus on chromosome 4 and, possibly, the major histocompatibility complex on chromosome 6.

Blood Group Antigens↗
PubMedDate not supplied

Increased cerebral blood flow during hypercapnia is not affected by lesion of the nucleus locus ceruleus.

To test the hypothesis that the putative noradrenergic innervation of intraparenchymal cerebral blood vessels from the nucleus locus ceruleus mediates the vasodilatory response to hypercapnia, regional cerebral blood flow was measured by iodo-[14C]antipyrine autoradiography in awake and restrained rats with unilateral 6-hydroxydopamine lesion of the nucleus locus ceruleus and in unlesioned control rats. Hypercapnia, induced by the inhalation of 5% or 8% CO2 in air for 8 minutes caused a 2 to 5-fold increase in regional cerebral blood flow. However, despite a marked reduction of about 90% in cortical norepinephrine levels ipsilateral to the lesion, blood flow to the frontal and parietal cortex, hippocampus, striatum and cerebellum increased to the same extent in ipsilateral and contralateral regions. Thus, lesion of the locus ceruleus and the resultant depletion of endogenous cortical and hippocampal norepinephrine, does not influence the cerebrovascular response to hypercapnia.

Animals↗
PubMedDate not supplied

[Polymorphism of the central region of D-loop of mitochondrial DNA and personality identification by forensic medicine methods].

Polymorphism of mDNA D-loop central region (CR), positions 16366-0072) was studied versus hypervariable sections (HVS1), positions 16024-16365, and HVS2, positions 00073-00340, for a sample of 71 residents of the Russian Federation. Ten polymorphic positions with 56 nucleotide substitutions, 55 of which are transitions, were detect in the CR section; no insertions or deletions were found there. It was proven as possible to use the mDNA CR locus as an additional identification marker in the forensic-expert of the mDNA control region. The probability of random coincidence (RC) of haplotypes in joint typing of HVS1, HVS2 and CR made 0.0208, which is 1.4-fold less versus the same parameter for haplotypes HVS1/HVS2 (RC = 0.0284).

Base Sequence↗
PubMed1994

[Effect of xylazine on acetylcholine content of the hippocampal CA1 region in urethane anesthetized rats].

By using acetylcholine selective microelectrode technique, a biphasic effect of xylazine on acetylcholine content of the hippocampal CA1 region in urethane anesthetized rats was observed as evidenced by the fact that small doses of xylazine (2.0 and 6.0 mg.kg-1) significantly increased, while higher dose (10.0 mg.kg-1) decreased the acetylcholine content. Though idazoxan (0.6 mg.kg-1) significantly antagonized the effect of xylazine when used in combination, the acetylcholine content in the hippocampal CA1 region of urethane anesthetized rats was still much lower than that of the control group. In rats whose nucleus locus coeruleus was chemically lesioned, xylazine (2.0 and 6.0 mg.kg-1) significantly decreased the acetylcholine content, and idazoxan (0.6 mg.kg-1), which increased the acetylcholine content in the hippocampal CA1 region when used alone, completely antagonized the effect of xylazine. These results suggest that the biphasic effect of xylazine and the lower than normal acetylcholine content observed when idazoxan was used to antagonize xylazine induced changes in acetylcholine content of the hippocampal CA1 region in urethane anesthetized rats might be related to the effects of xylazine and idazoxan on the central noradrenergic neurotransmitter system.

Acetylcholine↗
PubMed1991

Antibody in the CSF of patients with multiple system atrophy reacts specifically with rat locus ceruleus.

Idiopathic chronic autonomic dysfunction may occur as pure autonomic failure (PAF) or in association with multiple system atrophy (MSA). CSF immunoreactivity to rat locus ceruleus occurred in a significantly greater number of samples from MSA patients compared to control subjects or patients with PAF. Other brain regions infrequently showed immunoreactivity. These findings suggest that degeneration in MSA may release antigen(s) that induce antibodies against locus ceruleus neurons. Further studies are required to determine whether immune abnormalities play a pathogenetic role in MSA. Lack of CSF immunoreactivity in PAF is consistent with primarily peripheral involvement.

Adult↗
PubMed1987

Genetic organization of the agouti region of the mouse.

The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (Ay) and lethal light-bellied nonagouti (ax), are pseudoallelic. We present genetic data showing probable recombination between Ay and three agouti mutations (at, a, and ax), which suggest that Ay is a pseudoallele of the agouti locus. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to Ay provides a molecular access to genes at or near the agouti locus. However, previous studies suggested that the Emv-15 locus can recombine with some agouti alleles and therefore we analyzed mice from recombinant inbred strains and backcrosses to measure the genetic distance between various agouti alleles and the Emv-15 locus. Our data indicate that the Emv-15 locus is less than 0.3 cM from the agouti locus. These experiments provide a conceptual framework for initiating chromosome walking experiments designed to retrieve sequences from the agouti locus and give new insight into the genetic organization of the agouti region.

Animals↗
PubMed1987

Class I H-2Db determinants are not involved in hybrid resistance to parental H-2b/Hh-1b bone marrow allograft.

Hybrid resistance to parental H-2b bone marrow grafts is directed to a cell surface structure controlled by the Hh-1 locus in or near the H-2D region. The nature of this surface structure is not known. Since homozygosity at the class I H-2D locus or loci in this haplotype would seem a necessary but not sufficient condition for the grafts' susceptibility to resistance, we tested whether the expression of this phenotype is dependent on the expression of class I H-2Db determinants. Cloned variants of H-2b tumor RBL-5 were obtained by immunoselection for the absence of H-2Db expression, as determined by the inability to bind specific antibody and to induce or react with alloreactive cytotoxic T lymphocytes. The three clones used in this study were H-2Db negative but H-2Kb positive and were natural killer cell resistant. When tested in vivo as competitive inhibitors the variant cells were capable of blocking hybrid resistance to parental H-2b bone marrow grafts as were unselected H-2Db-positive parental line cells. Therefore, H-2Db expression is irrelevant for Hh-1b expression. An incidental observation was that YAC-1 cells, a non-H-2b tumor with pronounced susceptibility to natural killing, were able to block hybrid resistance. This reactivity, not observed in our previous studies, raises the possibility that at least some of the effector cells are cross-reactive or capable of dual recognition.

Animals↗
PubMed1991

Isodicentric X chromosome in a patient with Turner syndrome--implications for localization of the X-inactivation center.

Cytogenetic analyses have previously shown that the region Xq11.2-q21 is retained in all structurally abnormal X chromosomes. From these observations the conclusion has been drawn that this "critical region" on the proximal long arm of the X chromosome contains the locus controlling X-inactivation. Structurally abnormal X chromosomes without the X-inactivation center would allow nullisomy, disomy, or trisomy for genes on the X chromosome, and this condition is presumed nonviable. We studied a 28-year-old woman with primary amenorrhea and features of Turner syndrome who had an unusual isodicentric chromosome of the short arm of X. This patient provided us with the opportunity to more closely define the location of the X-inactivation center. High resolution chromosome analysis showed a 46,X,idic(X)(pter----q13.2::q13.2----pter) chromosome pattern in 94% of her cells and a 45,X complement in 6%. Replication studies showed this derivative X chromosome to be late-replicating (inactive) in all cells analyzed. DNA analysis confirmed the breakpoint of the isodicentric chromosome to be proximal to PGK1. Based on these results, the locus for the X-inactivation center can be refined to be within Xq11.2-q13.2.

Adult↗
PubMed1985

Activation of T lymphocytes results in an increase in H-2-encoded neuraminidase.

The endogenous neuraminidase activity of various mouse lymphoid subpopulations and tissue compartments was examined by a sensitive fluorometric assay. These analyses indicated that activated T lymphocytes possessed a significantly higher level of intracellular neuraminidase than activated B or resting T or B lymphocytes. Examination of the level of neuraminidase in bone marrow, thymus, lymph node, and unfractionated spleen indicated that these lymphoid tissues contained significantly less neuraminidase than was detected in stimulated T cells. Kinetic studies revealed that the majority of the increase in neuraminidase activity occurred between 24 and 48 h following stimulation. Analysis of activated T lymphocytes prepared from a panel of inbred mouse strains indicated that cells from mice of the H-2v haplotype, which possess the Neu-1a allele and are deficient in liver neuraminidase, exhibited a level of activity which was significantly lower than that detected in stimulated T cells from other mouse strains. These results indicate that the endogenous neuraminidase activity of T lymphocytes increases upon stimulation, and that the level of this enzyme activity in lymphoid cells is also controlled by the Neu-1 locus, which is located in the H-2 region of the major histocompatibility complex.

Animals↗
PubMed1995

Involvement of regions of the 4th and 7th chromosomes in the open-field activity of mice.

Reactivity to a new environment was studied in mice, using an open-field procedure in two strains, C57BL/6By and ABP/Le, the F1 populations and the intercrosses F2 and backcross segregating populations. The analysis of the behavioral traits: peripheral and central activities, leaning, rearing and defecation in the parental strains made it possible to show that the ABP/Le strain was more reactive than C57BL/6By. In addition, the study of segregating, for four phenotypic markers, in F2 and backcross populations strongly suggested that two autosomal regions were involved in the control of open-field behavior: one in chromosomal region comprising the b locus on chromosome 4 and one in chromosomal region comprising the p locus on chromosome 7.

Analysis of Variance↗
PubMed1980

Genetic control of murine IgD structural heterogeneity.

Murine B lymphocytes express two native forms of surface IgD: IgDI consists of two delta heavy chains and two light chains; IgDII consists of one heavy chain and one light chain. The relative amounts of IgDI and IgDII present on spleen cells were found to vary significantly among different strains of mice. Genetic evidence demonstrated that the IgDI/IgDII ratio is linked to the Igh-5 allotype. (The delta heavy chain is the product of the Igh-5 locus). Mice bearing the Igh-5e allotype have a low ratio, and mice bearing the Igh-5a or Igh-5b allotype have a high ratio. The Igh-5 locus and the gene controlling the IgDI/IgDII ratio appear to map to the region between the Igh-6 and Igh-V loci.

Animals↗