title: A new mouse mutant, skijumper.
abstract: 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.
authors.affiliation: Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London WCIN 3BG, UK.
authors.forename: Majid
authors.initials: M
authors.lastname: Hafezparast
authors.forename: Simon
authors.initials: S
authors.lastname: Ball
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Nicholson
authors.forename: Abi
authors.initials: A
authors.lastname: Witherden
authors.forename: Demet
authors.initials: D
authors.lastname: Arac
authors.forename: Neil
authors.initials: N
authors.lastname: Broadway
authors.forename: David
authors.initials: D
authors.lastname: Saggerson
authors.forename: Edwin
authors.initials: E
authors.lastname: Cooper
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Naase
authors.forename: Stephen
authors.initials: S
authors.lastname: Gokhale
authors.forename: Patti
authors.initials: P
authors.lastname: Quant
authors.forename: Carol
authors.initials: C
authors.lastname: Lascelles
authors.forename: Carole
authors.initials: C
authors.lastname: Nickols
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Baker
authors.forename: Josephine
authors.initials: J
authors.lastname: Peters
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Martin
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D006003:Glycogen; D020155:3-Hydroxybutyric Acid