Phenotypes Associated with This Genotype

Genotype
MGI:3530234

• Allelic Composition: Tg(HDexon1)62Gpb/0
• Genetic Background: involves: C57BL/6J * CBA/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:36689 )

• usually between 10 to 13 weeks of age

• mice can die suddenly

nervous system

seizures ( J:36689 )

• handling induced seizures that can be several minutes duration

decreased brain size ( J:36689 )

• average of 19% smaller than wildtype

behavior/neurological

limb grasping ( J:36689 )

• dyskinesia of limbs when suspended by the tail

tremors ( J:36689 )

• progressive resting tremor in limbs, trunk and head

• involuntary jerky shudders

impaired balance ( J:36689 )

• mice lose balance when sitting on hind limbs, turning and grooming their backs

stereotypic behavior ( J:36689 )

• onset of motor impairment as early as 4 weeks of age

• stereotypic repetitive stroking of the nose and face, hind limb kicking and scratching movement

abnormal vocalization ( J:36689 )

• 2 distinct characteristic vocalizations observed

seizures ( J:36689 )

• handling induced seizures that can be several minutes duration

endocrine/exocrine glands

abnormal pancreatic alpha cell morphology ( J:96353 )

• islets exhibit huntingtin inclusions in 24% of cells by 12 weeks of age

abnormal pancreatic beta cell morphology ( J:96353 )

• islets exhibit huntingtin inclusions in 19% of cells by 7 weeks of age, by week 12 frequency is greater than 95%

• islets are hypotrophic by 12 weeks, BrdU incorporation is reduced 6-fold

• significant reduction in insulin and somatostatin content by 12 weeks

• islets are smaller in size by 12 weeks

• islets contain few insulin secretory vesicles by 12 weeks

decreased pancreatic beta cell number ( J:96353 )

• by 12 weeks, no signs of apoptosis or necrosis are observed

abnormal pancreatic delta cell morphology ( J:96353 )

• islets exhibit huntingtin inclusions in 6% of cells by 12 weeks of age

small seminal vesicle ( J:36689 )

♂ • small seminal ducts and gland size

small ovary ( J:36689 )

♀

small testis ( J:36689 )

♂

growth/size/body

decreased body weight ( J:96353 )

• body weight declines after 10 weeks

weight loss ( J:36689 )

• body weight is normal at weaning

• with progression of phenotype up to 30% of body weight can be lost

• overall loss of muscle bulk observed

homeostasis/metabolism

abnormal glucose homeostasis ( J:96353 )

• abnormal glucose homeostasis

decreased circulating insulin level ( J:96353 )

• insulin secretion in response to glucose and KCl is decreased 4-fold and 2.5-fold, respectively, by 12 weeks of age

impaired glucose tolerance ( J:96353 )

• identified at 11.5 weeks of age, insulin response absent

renal/urinary system

polyuria ( J:36689 )

reproductive system

small seminal vesicle ( J:36689 )

♂ • small seminal ducts and gland size

small testis ( J:36689 )

♂

abnormal female reproductive system morphology ( J:36689 )

♀ • smaller size ovaries and uteri often observed

small ovary ( J:36689 )

♀

small uterus ( J:36689 )

♀

female infertility ( J:36689 )

♀

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:36689