Quantitative trait loci analysis of tail tendon break time in mice of C57BL/6J and DBA/2J lineage.

Tail tendon break time (TTBT), a measure of collagen cross-linking, shown to increase with age differs significantly among inbred strains of mice, indicating underlying genetic influences. This study was aimed to identify quantitative trait loci (QTLs) associated with tail tendon break time at three ages (200, 500, and 800 days of age) for 23 BxD recombinant inbred strains of mice and B6D2F(2) mice derived from C57BL/6J and DBA/2J strains. Heritability estimates were calculated, and QTL analyses were conducted using interval-mapping methods.

Gerald E. McClearn: complexity in behavior genetics.

A festskrift in honor of the career contributions of Gerald E. McClearn was held in State College, Pennsylvania in May 2009. A selection of papers presented at that celebration is included in this issue of Behavior Genetics.

Quantitative trait loci (QTL) analysis of longevity in C57BL/6J by DBA/2J (BXD) recombinant inbred mice.

Background And Aims: Genes associated with longevity have been identified using both single gene and genome-wide approaches in a variety of species. The aim of this study was to identify quantitative trait loci (QTLs) that influence longevity in male and female mice from twenty-three C57BL/6J by DBA/2J (BXD) recombinant inbred (RI) strains.

Methods: Approximately 12 animals of each sex for each RI strain were maintained under standard conditions until natural death or moribundity criteria were met.

Genomic analysis of variation in hindlimb musculature of mice from the C57BL/6J and DBA/2J lineage.

The precise locations of attachment points of muscle to bone-the origin and insertion sites-are crucial anatomical and functional characteristics that influence locomotor performance. Mechanisms that control the development of these interactions between muscle, tendon, and bone are currently not well understood. In a subset of BXD recombinant inbred (RI) strains derived from the C57BL/6J and DBA/2J strains, we observed a soleus femoral attachment anomaly (SFAA) that was rare in both parental strains (Lionikas, Glover et al.

Stability of genetic influences on pulmonary function in a longitudinal study of octogenarian twins.

Using data from the first four waves of the OCTO-Twin study (twins 80 + years), the present study investigated the stability and change of genetic and environmental contributions to pulmonary function. Using a genetic simplex model, variance in peak expiratory flow (PEF) at each wave was decomposed into additive genetic and nonshared (specific) environmental factors. Additionally, this analysis distinguished the source of these influences, either from previous waves (transmissions) or from novel influences at each wave (innovations).

Bone, muscle, and physical activity: structural equation modeling of relationships and genetic influence with age.

Correlations among bone strength, muscle mass, and physical activity suggest that these traits may be modulated by each other and/or by common genetic and/or environmental mechanisms. This study used structural equation modeling (SEM) to explore the extent to which select genetic loci manifest their pleiotropic effects through functional adaptations commonly referred to as Wolff's law. Quantitative trait locus (QTL) analysis was used to identify regions of chromosomes that simultaneously influenced skeletal mechanics, muscle mass, and/or activity-related behaviors in young and aged B6xD2 second-generation (F(2)) mice of both sexes.

Analysis of candidate genes and hypertension in African American adults.

Objective: We investigated the associations between hypertension status and the genotypes of four single nucleotide polymorphism (SNP) sites in four hypertension-related genes (Angiotensinogen [AGT], Angiotensin I Converting Enzyme [ACE], Angiotensinogen II receptor, subtype 1 [AGTR1], and Alpha 1-Antichymotrypsin [ACT or SERPINA3]), in an African American sample.

Methods: DNA from 628 participants of the Carolina African American Twin Study of Aging project, a population-based study of African American adult twins, was genotyped using SNPs shown to be associated with hypertension in other studies.

Results: The ACE SNP (ACE4 or A-240T) was associated with hypertension (P = .

Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences.

A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F(2) adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F(2) data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5.

Public statement: guidelines for the assessment and management of pain in rodents and rabbits.

The ACLAM Analgesia Task Force was appointed by ACLAM President Diane Gaertner in 2003. The charge to the Task Force was to develop guidelines that could be used by veterinarians, scientists and IACUCs in helping to provide appropriate assessment and management of pain in rodents, with the understanding that ultimately the clinical veterinarian on site at the institution must make decisions relevant to a specific animal or animals and/or protocol. The guidelines were not to be developed as, and should not be used as, requirements.

Dopamine receptor genes (DRD2, DRD3 and DRD4) and gene-gene interactions associated with smoking-related behaviors.

Cigarette smoking, like many addictive behaviors, has a genetic component, and the dopamine D2-like receptor genes (DRD2, DRD3 and DRD4) are candidates for contributing to these behaviors. Phenotypic information concerning smoking-related behaviors from a nationally representative sample of research volunteers was analyzed for association with polymorphisms in these genes. Genotype status at the DRD2 intron 2 simple tandem repeat was related to cigarettes per day (P = 0.

Refractometry for quality control of anesthetic drug mixtures.

Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels.

QTL analysis of trabecular bone in BXD F2 and RI mice.

Unlabelled: A sample of 693 mice was used to identify regions of the mouse genome associated with trabecular bone architecture as measured using microCT. QTLs for bone in the proximal tibial metaphysis were identified on several chromosomes indicating regions containing genes that regulate properties of trabecular bone.

Introduction: Age-related osteoporosis is a condition of major concern because of the morbidity and mortality associated with osteoporotic fractures in humans.

QTL influencing baseline hematocrit in the C57BL/6J and DBA/2J lineage: age-related effects.

Baseline serum hematocrit varies substantially in the population. While additive genetic factors account for a large part of this variability, little is known about the genetic architecture underlying the trait. Because hematocrit levels vary with age, it is plausible that quantitative trait loci (QTL) that influence the phenotype also show an age-specific profile.

Genetic determinants of weight of fast- and slow-twitch skeletal muscles in old mice.

The main goal of the study was to explore the genetic architecture underlying muscle weight in old mice. Weight of soleus, tibialis anterior (TA), extensor digitorum longus (EDL), and gastrocnemius muscles was measured in the C57BL/6J (B6) and DBA/2J (D2) strains and derivative generations: a panel of the BXD recombinant inbred (RI) strains and a B6D2 F(2) intercross at the age of 800 days. The between-strain difference in muscle weight (B6 > D2) ranged between 16% and 38%.

Anomaly of anatomical origin of soleus muscle: a mouse model.

In the laboratory mouse, the soleus muscle arises at the head of the fibula and inserts via the Achilles tendon on the tuber calcanei together with the gastrocnemius muscle. During routine dissection of mice from the BXD recombinant inbred (RI) strains, we found that the soleus often originated from the lateral epicondyle of the femur instead of the head of the fibula. This soleus femoral attachment anomaly (SFAA) changes the soleus from being a single-joint to a two-joint muscle.

Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice.

Quantitative trait locus (QTL) analyses were conducted to identify chromosomal regions that contribute to variability in serum alkaline phosphatase (AP) enzyme activity in mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains. Serum AP was measured in 400 B6D2 F2 mice at 5 mo and 400 B6D2 F2 mice at 15 mo of age that were genotyped at 96 microsatellite markers, and in 19 BXD recombinant inbred (RI) strains at 5 mo of age. A QTL on the distal end of chromosome 4 was present in all sex- and age-specific analyses with a peak logarithm of odds (LOD) score of 20.

An examination of early smoking experiences and smoking status in a national cross-sectional sample.

Aims: To extend previous work showing lightheadedness from and liking for smoking to be associated with continued smoking while controlling for demographics and social influences that can also contribute to progression to established smoking.

Design And Setting: Random digit dialing telephone survey conduced on 3383 never smokers, non-smokers, former smokers and current smokers in the continental United States.

Measurements: Demographic information (sex, race, age, education level), smoking history, reactions to early experiences with smoking (lightheadedness, liking), whether parents, siblings or friends smoked when respondent was a teenager.

Effects of periadolescent ethanol exposure on alcohol preference in two BALB substrains.

Ethanol exposure during adolescence is a rite of passage in many societies, but only a subset of individuals exposed to ethanol becomes dependent on alcohol. To explore individual differences in response to ethanol exposure, we compared the effects of periadolescent ethanol exposure on alcohol drinking in an animal model. Male and female mice of two BALB substrains were exposed to ethanol in one of three forms--choice [water vs.

Adjusting data to body size: a comparison of methods as applied to quantitative trait loci analysis of musculoskeletal phenotypes.

Unlabelled: The aim of this study was to compare three methods of adjusting skeletal data for body size and examine their use in QTL analyses. It was found that dividing skeletal phenotypes by body mass index induced erroneous QTL results. The preferred method of body size adjustment was multiple regression.

The Washington University Twin Study of alcoholism.

Genetic contributions to the liability to develop alcoholism in males of Northern and Western European ancestry are well-established. However, questions remain concerning the role of genetic variation in the etiology of alcoholism among non-white populations, among women, and the possibility of etiological heterogeneity in subtypes of alcoholism. The answers to these questions are needed to help define phenotypes for molecular genetic studies searching for QTLs for alcoholism.

Neutrophil-mediated accumulation of 2-ClHDA during myocardial infarction: 2-ClHDA-mediated myocardial injury.

The pathophysiological sequelae of myocardial infarction include neutrophil infiltration into the infarct zone that contributes to additional damage to viable tissue and removal of cellular debris from necrosed tissue. Reactive chlorinating species produced by myeloperoxidase amplify the oxidant capacity of activated neutrophils. Plasmalogens are a major phospholipid subclass of both endothelial cells and cardiac myocytes.

Quantitative trait loci analysis of structural and material skeletal phenotypes in C57BL/6J and DBA/2 second-generation and recombinant inbred mice.

Unlabelled: QTL analyses identified several chromosomal regions influencing skeletal phenotypes of the femur and tibia in BXD F2 and BXD RI populations of mice. QTLs for skeletal traits co-located with each other and with correlated traits such as body weight and length, adipose mass, and serum alkaline phosphatase.

Introduction: Past research has shown substantial genetic influence on bone quality, and the impact of reduced bone mass on our aging population has heightened the interest in skeletal genetic research.

A preliminary report on the effects of paclitaxel-impregnated stents on sheep nasal mucosa.

Introduction: Traditional frontal sinus stents serve only as mechanical devices. It has been proposed that stents also may serve as drug-delivery systems for the topical application of drugs that minimize postoperative scarring. Paclitaxel (Taxol), which has recognized antiscarring effects, may be incorporated via a polymeric formulation into standard rubber stents.

Combined association and linkage analysis applied to the APOE locus.

Combined association and linkage analysis is a powerful tool for pinpointing functional quantitative traits (QTLs) responsible for regions of significant linkage identified in genome-wide scans. We applied this technique to apoE plasma levels and the APOEepsilon2/epsilon3/epsilon4 polymorphism in two Dutch twin cohorts of different age ranges. Across chromosome 19, short tandem repeats and the APOEepsilon2/epsilon3/epsilon4 polymorphism were genotyped in adolescent (aged 13-22 years) and adult (aged 34-62 years) Dutch twins.