title: Sexual dysfunction and sudden death in epileptic male EL mice: inheritance and prevention with the ketogenic diet.
abstract: OBJECTIVE
  The EL mouse is an animal model for multifactorial idiopathic epilepsy. Although EL mice have been studied extensively for >45 years, the etiology of male sudden death and its relation to seizures have not been defined. Here we investigated the cause of EL male sudden death and its relation to epilepsy.
  
  
  METHODS
  For histopathologic analysis, the terminally ill EL mice (n = 15) were killed, and the tissues were fixed. Blood chemical composition was compared between the terminally ill EL (n = 9) and the healthy age-matched EL (n = 17) and DDY (n = 11) males. To determine the effect of the ketogenic diet (KD) on sudden male death, young male EL mice (P30) were randomly separated into two groups that were fed ad libitum with either Agway lab chow (control n = 38) or with the KD (treated, n = 39) for 5 months. The genetic predisposition to sudden death was analyzed in the backcross generation (n = 106) of a cross between EL and the nonepileptic ABP strains.
  
  
  RESULTS
  Sudden death coincided with the onset of seizures (70-80 days) and affected 94% of male EL mice by age 300 days. Urethral plugs were observed histologically in 13 of 15 longitudinally sectioned penises. Concentrations of blood urea nitrogen, creatinine, phosphorus, and calcium in the terminally ill mice were significantly elevated when compared with those of healthy animals. None of the mice treated with the KD experienced sudden death, whereas 15 (39%) of the untreated control mice died by age 5 months. The sudden death in male EL mice was inherited as an autosomal recessive sex-limited lethal trait.
  
  
  CONCLUSIONS
  The cause of sudden death in male EL mice arises from abnormal ejaculation, which produces a urethral plug with consequent urinary retention and acute severe uremia. The coincident onset of seizures and sudden death in EL males suggests that a sexual dysfunction is associated with epilepsy in this model.
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts 02167, USA.
authors.forename: Mariana T
authors.initials: MT
authors.lastname: Todorova
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dangler
authors.forename: Michael G
authors.initials: MG
authors.lastname: Drage
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sheppard
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Seyfried
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D002869:Chromosome Aberrations; D003433:Crosses, Genetic; D003645:Death, Sudden / Q000473:pathology / Q000517:prevention & control*; D004041:Dietary Fats / Q000008:administration & dosage*; D004198:Disease Susceptibility; D004542:Ejaculation / Q000235:genetics* / Q000502:physiology; D004573:Electrolytes / Q000097:blood; D017029:Epilepsy, Complex Partial / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D004829:Epilepsy, Generalized / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D018598:Minisatellite Repeats / Q000235:genetics; D010413:Penis / Q000473:pathology; D012726:Sexual Behavior, Animal / Q000502:physiology*; D012735:Sexual Dysfunction, Physiological / Q000235:genetics / Q000517:prevention & control*; D014511:Uremia / Q000235:genetics / Q000473:pathology; D014521:Urethra / Q000473:pathology; D014524:Urethral Obstruction / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D016055:Urinary Retention / Q000235:genetics / Q000473:pathology / Q000517:prevention & control
chemical_list: D004041:Dietary Fats; D004573:Electrolytes; D005819:Genetic Markers