A new mouse mutant, skijumper.
Low blood sugar levels are a well-known cause of severe illness and often death in newborn humans, especially those that are small for age. Few of the causes of neonatal hypoglycemia are known, and many remain to be found. We describe a novel mouse mutant, skijumper (skimp), in which pups, despite feeding well, have low levels of glucose and develop opisthotonos, followed by death typically within a few days after birth. Genetic mapping studies have localized the lesion to a approximately 1 cM interval on mouse Chromosome (Chr) 7 between D7Mit318 and D7Mit93. We have carried out extensive analysis to define the phenotype and its likely cause. In addition to low blood glucose, affected skijumper mice have lowglycogen and ketone levels. Mass spectrometric analysis of blood samples has excluded major defects in amino acid metabolism. Initial biochemical analyses suggested a defect in ketogenesis as one possible cause of this phenotype. However, measurements of levels and activities of carnitine, carnitine palmitoyl transferases, and other enzymes involved in ketogenesis, along with studies of mitochondrial structure and function, did not demonstrate significant differences between skijumper, unaffected littermates, and control wild-type mice. These results indicate that abnormal enzyme activity in known pathways does not appear to be the primary biochemical lesion in skijumper. The skijumper may be a new valuable model for studying and understanding one type of neonatal morbidity and death.
Hafezparast
Majid
M
Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London WCIN 3BG, UK.
Ball
Simon
S
Nicholson
Sharon J
SJ
Witherden
Abi
A
Arac
Demet
D
Broadway
Neil
N
Saggerson
David
D
Cooper
Edwin
E
Naase
Mahmoud
M
Gokhale
Stephen
S
Quant
Patti
P
Lascelles
Carol
C
Nickols
Carole
C
Baker
Cathy S
CS
Peters
Josephine
J
Martin
Joanne E
JE
Fisher
Elizabeth M C
EM
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D006003:Glycogen / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D040582:Inheritance Patterns; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics* / Q000528:radiation effects; D010641:Phenotype; D016133:Polymerase Chain Reaction
D001786:Blood Glucose; D006003:Glycogen; D020155:3-Hydroxybutyric Acid