TY  - CHAP
M1  - Book, Section
TI  - Mouse Models of Human Genetic Disorders
A1  - Craigen, William J.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.313
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - The  mouse,  as  a  prototypical  mammal,  has  been  the  subject  of  systematic  experimental  investigation  for  the  last  century.  An  ever-enlarging  number  of  mouse  mutations  exist  that  provide  models  for  human  genetic  disorders,  and  the  mouse  has  become  an  increasingly  important  tool  for  dissecting  the  molecular  basis  of  common  acquired  disease  states.  The  most  frequently  used  approaches  to  modifying  the  mouse  genome  are  microinjection  of  purified  DNA  and  homologous  recombination  in  embryonic  stem  cells.The  laboratory  mouse  provides  a  number  of  advantages  as  an  experimental  system.  It  is  small  and  hence  inexpensive  to  keep  under  well-controlled  environmental  conditions.  Mice  produce  abundant  offspring  following  a  short  gestation,  allowing  for  large  sample  sizes,  and  there  exist  numerous  inbred  strains  available  for  selective  breeding  strategies.  The  mouse  shares  many  metabolic  and  developmental  pathways  with  humans,  and  there  are  syntenic  relationships  over  much  of  its  genome  that  correspond  to  those  of  humans.  Numerous  reagents  exist  for  gene  mapping  and  identification,  and  because  of  historic  interests,  there  are  frequently  multiple  alleles  at  a  given  locus.  Complex  genetic  interactions  can  be  examined  using  selected  compound  alleles,  double  mutations,  and  strain-specific  modifiers.  Genetic  mechanisms  such  as  haploinsufficiency,1  digenic  inheritance,2  and  imprinting,3,4  can  be  experimentally  dissected  in  the  mouse.Mice  can  also  be  used  as  recipients  for  human  tissues  such  as  bone  marrow,  and  can  be  genetically  “humanized”  via  the  introduction  of  human  alleles,  whether  disease  associated  or  conferring  disease  resistance.  This  may  represent  single  genes  or  more  recently  large  regions  of  DNA,  and  even  chromosomal  fragments.  The  development  of  standardized  behavioral  testing  and  an  ever-expanding  understanding  of  mouse  behavior  has  provided  a  means  for  defining  the  genetic  and  molecular  basis  of  learning  and  memory,  an  increasingly  achievable  goal  for  the  future.  The  mouse  is  also  a  unique  resource  for  the  development  of  phenotype  driven  genetic  screens  for  mutant  genes  when  mutagenesis  is  coupled  to  a  standardized  battery  of  assessments  such  as  behavioral,  sensory,  biochemical,  and  physiological  testing.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.313
Y2  - 2024/04/18
UR  - ommbid.mhmedical.com/content.aspx?aid=1181402868
ER  -