The power of comparative and developmental studies for mouse models of Down syndrome

Since the genetic basis for Down syndrome (DS) was described, understanding the causative relationship between genes at dosage imbalance and phenotypes associated with DS has been a principal goal of researchers studying trisomy 21 (Ts21). Though inferences to the gene-phenotype relationship in humans have been made, evidence linking a specific gene or region to a particular congenital phenotype has been limited. To further understand the genetic basis for DS phenotypes, mouse models with three copies of human chromosome 21 (Hsa21) orthologs have been developed. Mouse models offer access to every tissue at each stage of development, opportunity to manipulate genetic content, and ability to precisely quantify phenotypes. Numerous approaches to recreate trisomic composition and analyze phenotypes similar to DS have resulted in diverse trisomic mouse models. A murine intraspecies comparative analysis of different genetic models of Ts21 and specific DS phenotypes reveals the complexity of trisomy and important considerations to understand the etiology of and strategies for amelioration or prevention of trisomic phenotypes. By analyzing individual phenotypes in different mouse models throughout development, such as neurologic, craniofacial, and cardiovascular abnormalities, greater insight into the gene-phenotype relationship has been demonstrated. In this review we discuss how phenotype-based comparisons between DS mouse models have been useful in analyzing the relationship of trisomy and DS phenotypes

Latissimus dorsi transfer for the treatment of massive tears of the rotator cuff

The objective of this paper was to determine the outcome of the transfer of the latissimus dorsi tendon in patients with massive irreparable rotator cuff tears. Eighteen patients of mean age 54 years (range 37–72 years) with massive irreparable rotator cuff tears were studied. The mean follow-up was 28 months (range 12–58 months). The postoperative Constant score was higher by an average of 21.15 points compared to the preoperative score (P=0.002); 88.8% of patients reported significant pain relief and improved mobility, particularly on external rotation. Postoperative resting antero-posterior radiography in neutral rotation revealed a mean 3.2-mm depression of the humeral head, due to the tenodesis effect of tendon transfer, thus, increasing the deltoid lever arm. These clinical results suggest that latissimus dorsi transfer is a useful surgical technique for treating massive irreparable postero-superior tears of the rotator cuff in young and/or active patients, providing significant pain relief and improved shoulder strength