ABSTRACT
The analysis of lethal phenotypes in developing mice not only spans the prenatal period but also encompasses the time from birth to sexual maturity. This underappreciated fact is supported by the anatomic equivalence of the mouse brain at postnatal day (PND) 7 to that of the human infant brain at birth67,68 as well as the myriad functional and structural changes that occur as a neonatal mouse evolves from a bald, blind, nearly sessile pinkie (PND 0) to a haired, mobile juvenile at weaning (PND 21 or PND 22) and nally a sexually capable animal at puberty (about PND 28 to PND 35, depending on the sex and strain/stock). Therefore, the tendency of some researchers to ignore postnatal lesions when assessing a developmental phenotype is ill-advised. The choice of parameters to examine and the methods used in the analysis will differ depending on the developmental age of the subjects, the presumed timing of the lethal event(s), and in many instances the expertise and interest of the researchers tasked with conrming the existence and dening the nature of lethal developmental phenotypes. However, the search for novel
Analysis of Cells, Tissues, and Organs from Developing Mice ............................................................ 294 Macroscopic Analysis ....................................................................................................................... 294 Microscopic Analysis ........................................................................................................................ 297
Histological Processing ................................................................................................................ 297 Histopathologic Assessment ........................................................................................................ 297
Ultrastructural Evaluation ................................................................................................................. 300 Special Methods for Morphological Assessment .............................................................................. 300 Scoring Strategies for Developmental Pathology Analyses .............................................................. 300 Resources for Structural Analysis ..................................................................................................... 301
General Patterns of Damage Observed in Developing Mice ................................................................. 302 Common Developmental Pathology Phenotypes and Their Specic Causes and Timing ..................... 303
Prenatal Lethality .............................................................................................................................. 303 Postnatal Lethality ............................................................................................................................ 307 Strain-Based Differences in Responsiveness .................................................................................... 307 Sex-Based Differences in Responsiveness ........................................................................................ 309 Lethality with Variable Penetrance ....................................................................................................310 Dominant Phenotypes ........................................................................................................................311 Maternal Impact on Developmental Phenotypes ...............................................................................313
Developmental Responses to Injury .......................................................................................................314 Basic Reactions to Damage during Development ..............................................................................314 Background Incidences of Birth Defects in Developing Mice ..........................................................318 Linked Developmental Defects ......................................................................................................... 323
Summary ................................................................................................................................................ 324 Appendix ................................................................................................................................................ 324 References ...............................................................................................................................................332
phenotypes should be undertaken by using multiple techniques-including anatomic pathology, clinical pathology, and molecular pathology tools-because more new conditions will be discovered by casting a wider net.449
