Several bone morphogenetic proteins (BMPs) are expressed in the apical ectodermal ridge (AER), a critical signaling center that directs the outgrowth and patterning of limb mesoderm, but little is known about their function. To study the functions of apical ectodermal BMPs, an AER-specific promoter element from the Msx2 gene was used to target expression of the potent BMP antagonist noggin to the apical ectoderm of the limbs of transgenic mice. Msx2-noggin mutant mice have severely malformed limbs characterized by syndactyly, postaxial polydactyly, and dorsal transformations of ventral structures indicated by absence of ventral footpads and presence of supernumerary ventral nails. Mutant limb buds exhibit a dorsoventral (DV) and anteroposterior (AP) expansion in the extent of the AER. AER activity persists longer than normal and is maintained in regions of the apical ectoderm where its activity normally ceases. Mutant limbs possess a broad band of mesodermal tissue along the distal periphery that is absent from normal limbs and which fails to undergo the apoptosis that normally occurs in the subectodermal mesoderm. Taken together, our results suggest that apical ectodermal BMPs may delimit the boundaries of the AER by preventing adjacent nonridge ectodermal cells from becoming AER cells; negatively modulate AER activity and thus fine-tune the strength of AER signaling; and regulate the apoptosis of the distal subectodermal mesoderm that occurs as AER activity attenuates, an event that is essential for normal limb development. Our results also confirm that ectodermal BMP signaling regulates DV patterning.

No abstract

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for over 5,000 genes from targeted embryonic stem cells on the C57BL/6N genetic background. This includes 2,850 null alleles for which no equivalent mutant mouse line exists, 2,987 novel conditional-ready alleles, and 4,433 novel reporter alleles. This nearly triples the number of genes with reporter alleles and almost doubles the number of conditional alleles available to the scientific community. When combined with more than 30 years of community effort, the total mutant allele mouse resource covers more than half of the genome. The extensively validated collection is archived and distributed through public repositories, facilitating availability to the worldwide biomedical research community, and expanding our understanding of gene function and human disease.

A successful embryo transfer depends on the quality of the transferred embryos, recipients, and the transfer techniques. Among these, transfer techniques are often the limiting factor because transfer methodologies and personal skills vary. Suboptimal embryo transfer procedures can compromise transgenic experiments (pronuclear microinjection and gene targeting) and critical steps of mouse colony maintenance (embryo cryopreservation and mouse line rederivation). Here we present an efficient and simple procedure utilizing specific designs to improve the transfer quality. A 100% implantation rate is observed after the utero-tubal embryo transfer, which indicates that the modified method successfully prevents the embryos from flowing out of the punctured hole during embryo transfer. We believe this alternative methodology is able to fulfill the need of high efficiency of animal production.