Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.

Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.

Hair whorl patterns on the bovine forehead may be related to breeding soundness measures.

The objective of this study was to determine if there is an association between facial hair whorl patterns on the bovine forehead and sperm morphology. Breeding soundness exams were conducted on 219 yearling bulls at three Colorado State University facilities. There were 150 Angus bulls and the remaining bulls were of several different breeds. Hair whorl patterns on the forehead were classified as round or nonround epicenters. Angus bulls with round epicenters had a higher percentage of morphologically normal spermatozoa compared to nonround epicenters (P < 0.05). Hair whorls on Angus bulls were sorted into two extreme groups of round spirals, with rotation or long lines that were longer than the width of the eyes. Bulls with round spirals had a greater percentage of normal spermatozoa compared to bulls with long lines (P < 0.05). Hair whorl pattern on Angus bulls also had an effect on the percentage of bulls that had the minimum threshold value of 70% normal spermatozoa. Eighty percent of Angus bulls with round epicenters had > 70% or more normal spermatozoa compared to 59% with a nonround epicenter (P < 0.01). Fifty percent of Angus bulls with long lines failed because they had < 70% normal spermatozoa. There were no significant differences in the remaining non-Angus bulls. Hair whorl patterns may be useful for making early culling decisions.