Abstract
The International Knockout Mouse Consortium was formed in 2007 to inactivate (“knockout”) all protein-coding genes in the mouse genome in embryonic stem cells. Production and characterization of these mice, now underway, has generated and phenotyped 3,100 strains with knockout alleles. Skin and adnexa diseases are best defined at the gross clinical level and by histopathology. Representative retired breeders had skin collected from the back, abdomen, eyelids, muzzle, ears, tail, and lower limbs including the nails. To date, 169 novel mutant lines were reviewed and of these, only one was found to have a relatively minor sebaceous gland abnormality associated with follicular dystrophy. The B6N(Cg)-Far2tm2b(KOMP)Wtsi/2J strain, had lesions affecting sebaceous glands with what appeared to be a secondary follicular dystrophy. A second line, B6N(Cg)-Ppp1r9btm1.1(KOMP)Vlcg/J, had follicular dystrophy limited to many but not all mystacial vibrissae in heterozygous but not homozygous mutant mice, suggesting that this was a nonspecific background lesion. We discuss potential reasons for the low frequency of skin and adnexal phenotypes in mice from this project in comparison to those seen in human Mendelian diseases, and suggest alternative approaches to identification of human disease-relevant models.
Highlights
IntroductionThese questions, simple to articulate, have complex answers at best, but are predicated on our knowledge of gene function and more importantly the pleiotropic functions of genes, which can only be elucidated though experimentation and through genetic manipulation
How many genes are involved in the normal ontogeny and physiology of the skin and its adnexal structures? How do they interact and how are they controlled? These questions, simple to articulate, have complex answers at best, but are predicated on our knowledge of gene function and more importantly the pleiotropic functions of genes, which can only be elucidated though experimentation and through genetic manipulation
We have investigated the apparent deficiency of skin and adnexal phenotypes in a random set of strains from a systematic, genome-wide, knockout study using histopathological phenotyping
Summary
These questions, simple to articulate, have complex answers at best, but are predicated on our knowledge of gene function and more importantly the pleiotropic functions of genes, which can only be elucidated though experimentation and through genetic manipulation. How many genes are involved in the normal ontogeny and physiology of the skin and its adnexal structures? Faced with this challenge, we might initially search major databases such as Mouse Genome Informatics (MGI; http://www.informatics.jax.org/), Online Mendelian Inheritance in Man We might initially search major databases such as Mouse Genome Informatics (MGI; http://www.informatics.jax.org/), Online Mendelian Inheritance in Man (https://www.omim. org/), or Orphanet (http://www.orpha.net/) and ask whether naturally-occurring or genetically
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
