Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad4 Knockout Using Collaborative Cross Mouse Population.

Obesity and its attendant conditions have become major health problems worldwide, and obesity is currently ranked as the fifth most common cause of death globally. Complex environmental and genetic factors are causes of the current obesity epidemic. Diet, lifestyle, chemical exposure, and other confounding factors are difficult to manage in humans. The mice model is helpful in researching genetic BW gain because genetic and environmental risk factors can be controlled in mice. Studies in mouse strains with various genetic backgrounds and established genetic structures provide unparalleled opportunities to find and analyze trait-related genomic loci. In this study, we used the Collaborative Cross (CC), a large panel of recombinant inbred mouse strains, to present a predictive study using heterozygous Smad4 knockout profiles of CC mice to understand and effectively identify predispositions to body weight gain. Male C57Bl/6J Smad4+/- mice were mated with female mice from 10 different CC lines to create F1 mice (Smad4+/-x CC). Body weight (BW) was measured weekly until week 16 and then monthly until the end of the study (week 48). The heritability (H2) of the assessed traits was estimated and presented. Comparative analysis of various machine learning algorithms for predicting the BW changes and genotype of mice was conducted. Our data showed that the body weight records of F1 mice with different CC lines differed between wild-type and mutant Smad4 mice during the experiment. Genetic background affects weight gain and some lines gained more weight in the presence of heterozygous Smad4 knockout, while others gained less, but, in general, the mutation caused overweight mice, except for a few lines. In both control and mutant groups, female %BW had a higher heritability (H2) value than males. Additionally, both sexes with wild-type genotypes showed higher heritability values than the mutant group. Logistic regression provides the most accurate mouse genotype predictions using machine learning. We plan to validate the proposed method on more CC lines and mice per line to expand the literature on machine learning for BW prediction.

Systems genetics analysis of oral squamous cell carcinoma susceptibility using the mouse model: current position and new perspective.

Oral squamous cell carcinoma (OSCC) is one of the most common human malignancies with complex etiology and poor prognosis. Although environmental carcinogens and carcinogenic viruses are still considered the main etiologic factors for OSCC development, genetic factors obviously play a key role in the initiation and progression of this neoplasm, given that not all individuals exposed to carcinogens develop the same severity of the disease, if any. Identifying genetic loci modulating OSCC risk may have several important clinical implications, including early detection, prevention and developing new treatment strategies. Due to limitations in controlled and standardized genetic studies in humans, genetic components underlying susceptibility of OSCC development remain largely unknown. A combination of quantitative trait loci mapping in mice, with complementary association studies in humans, has the potential to discover novel cancer risk loci. As of today, a limited number of genetic analyses were applied on rodent models to locate novel genetic loci associated with human OSCC. Here, we discuss the current status of the mouse models use for dissecting the genetic basis of OSCC and highlight how systems genetics analysis using mouse models, may increase our understanding of human OSCC susceptibility.

Allograft and Collagen Membrane Augmentation Procedures Preserve the Bone Level around Implants after Immediate Placement and Restoration.

Background: Immediate implant placement and restoration (IPR), is a reliable treatment modality. Purpose: This historical prospective study evaluated the medium-term outcomes of hard tissue after IPR in the anterior maxilla with simultaneous hard tissue augmentation. Methods: Seventy-three patients treated with single-implant IPR in the anterior maxilla were followed for 1-8 years. Treatment involved, atraumatic extraction, immediate implant placement and abutment adaptation, followed by simultaneous augmentation with mineralized freeze-dried bone allograft (FDBA) particles to fill the gaps and restore the ridge. The surgical site was stabilized with a resorbable collagen membrane, followed by the connection of an acrylic provisional restoration. Results: All implants osseointegrated during the follow-up period (mean, 34 ± 22 months). Radiographic evaluation of the distance between the implant shoulder (IS) and crestal bone level (CBL) was of 0.86 ± 0.86 mm and 0.8 ± 0.84 mm mesially and distally, respectively. Splitting the results into up to 3 years and 3-8 years of follow-up data, the corresponding values were 0.90 ± 0.83 and 0.68 ± 0.88 for the mesial aspect and 0.99 ± 0.87and 0.74 ± 0.83 for the distal aspect, respectively. Mean peri-implant probing depth was 3.63 mm (SD ± 1.06) and 16 implants (22%) presented at least one bleeding pocket of ≥5 mm (peri implant mucositis). Conclusions: The immediate replacement of a single maxillary tooth by implants combined with guided bone regeneration is a predictable treatment modality with favorable peri-implant bony response.