All Phenotypes Htr2c<tm1Jul> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
ot1	Htr2c^tm1Jul/Y	B6.129S-Htr2c^tm1Jul	MGI:3789135
ot2	Htr2c^tm1Jul/Y	either: (involves: 129S2/SvPas * C57BL/6J * DBA/2) or (involves: 129S4/SvJae * C57BL/6J * DBA/2)	MGI:2175216

Allelic Composition	Htr2c^tm1Jul/Y
Genetic Background	B6.129S-Htr2c^tm1Jul

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htr2c^tm1Jul mutation (1 available); any Htr2c mutation (12 available)

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

behavior/neurological

abnormal response to new environment ( J:51567 )

• hemizygotes show reduced aversion to a novel environment; the latencies to emerge from a small dark enclosure into a brightly lit open field are reduced in mutants compared to wild-type

abnormal spatial learning ( J:51567 )

• hemizygotes show abnormal performance in the Morris water maze, failing to show a preference for the trained site in probe trials following training

• however, contextual conditioning is normal

polyphagia ( J:50262 )

• both young (12-14 weeks) and older (39-43 weeks) male hemizygotes show a significant increase in daily food intake relative to wild-type controls

• however, no significant differences are observed in plasma glucose, corticosterone, triglycerides or FFAs at either age

adipose tissue

increased white adipose tissue amount ( J:50262 )

• on a standard chow diet, male hemizygotes show an age-dependent increase in white adipose tissue (WAT) deposits relative to wild-type controls

• at 39-43 weeks of age, epididymal, perirenal and subcutaneous WAT weights are increased by 40-64% relative to wild-type levels

increased epididymal fat pad weight ( J:50262 )

• at 39-43 weeks of age

increased renal fat pad weight ( J:50262 )

• at 39-43 weeks of age

growth/size/body

increased susceptibility to age related obesity ( J:50262 )

• on a standard chow diet, male hemizygotes develop late onset obesity at >20 weeks of age

• by 42 weeks of age, hemizygotes show a ~30% increase in body weight relative to wild-type controls

increased susceptibility to diet-induced obesity ( J:50262 )

• when fed a high-fat diet for 9 weeks, male hemizygotes display a significantly higher gain weight than similarly treated wild-type mice; however, no differences in plasma FFA or triglyceride levels are observed

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:50262 )

hyperglycemia ( J:50262 )

• when fed a high-fat diet for 9 weeks, male hemizygotes display plasma glucose levels in the diabetic range (>300 mg/dl); however, no hyperlipidemia is observed

increased circulating insulin level ( J:50262 )

• at 39-43 weeks of age, male hemizygotes display a 7-fold increase in plasma insulin levels relative to wild-type controls; however, plasma insulin levels are normal at 12-14 weeks of age

• when fed a high-fat diet for 9 weeks, male hemizygotes display hyperinsulinemia relative to similarly treated wild-type mice

increased circulating leptin level ( J:50262 )

• at 39-43 weeks of age, male hemizygotes display a 2.5-fold increase in plasma leptin levels relative to wild-type controls; however, plasma leptin levels are normal at 12-14 weeks of age

• when fed a high-fat diet for 9 weeks, male hemizygotes display hyperleptinemia relative to similarly treated wild-type mice

impaired glucose tolerance ( J:50262 )

• at 120 min after a single i.p. injection of D-glucose (1 gm/kg), obese male hemizygotes display significantly higher blood glucose levels than wild-type controls, indicating impaired glucose tolerance

insulin resistance ( J:50262 )

• after a 6 hr fast, 42-58 week old (obese) male hemizygotes show both hyperinsulinemia and mildly increased blood glucose levels, indicating insulin resistance

abnormal tumor necrosis factor level ( J:50262 )

• obese hemizygotes display markedly increased white adipose tissue TNF mRNA levels, despite normal plasma FFA and corticosterone levels

abnormal response/metabolism to endogenous compounds ( J:50262 )

• following an i.p. injection of 2.5 mg/kg of leptin, 38-46 week old male hemizygotes mice exhibit a smaller decrease in food intake and body weight relative to wild-type controls; however, leptin resistance can be overcome by a higher dose (5 mg/kg) and is therefore only partial in obese hemizygotes

• no differences in the effects of either leptin dose (2.5 or 5 mg/kg) on food intake and body weight are observed in younger male hemizygotes at 11-13 weeks of age

nervous system

reduced long-term potentiation ( J:51567 )

• selective impairment of long-term potentiation restricted to medial perforant path-dentate gyrus synapses of mutants, indicating perturbed dentate gyrus function

immune system

abnormal tumor necrosis factor level ( J:50262 )

• obese hemizygotes display markedly increased white adipose tissue TNF mRNA levels, despite normal plasma FFA and corticosterone levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:50262

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

mortality/aging

premature death ( J:24339 )

• male hemizygotes are prone to sudden death from seizures

• spontaneous deaths are first observed in the fifth week after birth

• survival rate continues to decline thereafter, such that less than 60% survival is noted at 25 weeks of age

• however, deaths are not preceded by any obvious health problems

growth/size/body

increased body weight ( J:24339 )

• male hemizygotes show a 13% increase in average total body mass relative to wild-type controls, with no difference in body length

• in rare cases, male hemizygotes weigh twice as much as wild-type siblings, attaining a weight of up to 82 g

• when fed ad libitum, male hemizygotes weigh significantly more than wild-type controls, with no significant changes in body length

• however, when pair-fed for 4 weeks postweaning and fasted overnight, male hemizygotes that have been provided only the amount of food consumed by their wild-type partners show no differences in body mass, length, white adipose tissue deposits, or plasma glucose and insulin levels relative to wild-type littermates that have been fed ad libitum

adipose tissue

increased white adipose tissue amount ( J:24339 )

• male hemizygotes display significantly larger white adipose tissue deposits than wild-type controls

• in contrast, brown adipose tissue weights are not significantly altered

increased epididymal fat pad weight ( J:24339 )

• male hemizygotes show a >30% increase in epididymal white adipose tissue deposits relative to wild-type controls

increased renal fat pad weight ( J:24339 )

• male hemizygotes show a 48% increase in perirenal white adipose tissue deposits relative to wild-type controls

behavior/neurological

behavior/neurological phenotype ( J:24339 )

N	• hemizygous males display normal sensitivity to thermal and mechanical nociceptive stimuli relative to wild-type controls

increased susceptibility to pharmacologically induced seizures ( J:24339 )

• in response to i.v. infusion of metrazol (an epileptogenic GABA_A receptor antagonist) at a constant rate, 11-15 week old male hemizygotes display a 24% reduction in seizure threshold (onset of first twitch response), an 83% decrease in the duration of the tonic-clonic phase, and a 48% decrease in the lethal dose, relative to wild-type controls

impaired behavioral response to xenobiotic ( J:24339 )

• o unlike wild-type controls where i.p. admninistration of the serotonergic agonist m-chlorophenylpiperazine (mCPP, 5 mg/kg) reduces food intake by 78%, male hemizygotes are resistant to the appetite suppresant (anorectic) actions of mCPP

polyphagia ( J:24339 )

• male hemizygotes display increased food consumption as a result of a behavioral disorder rather than a metabolic defect

increased grooming behavior ( J:24339 )

• spontaneous seizures are often preceded by repetitive grooming of the snout

tonic seizures ( J:24339 )

• occasionally, seizures progress to a tonic extension phase, resulting in respiratory arrest and death within seconds of seizure onset

tonic-clonic seizures ( J:24339 )

• after the initial repetitive grooming activity, male hemizygotes fall on their sides and progress to hyperkinetic tonic-clonic seizures

• in most cases, hemizygotes recover quickly and resume a normal behavior; this cycle may be repeated over the next few minutes

sporadic seizures ( J:24339 )

• male hemizygotes display spontaneous epileptic seizures, with a frequency not greater than 2 or 3 per day