All Phenotypes Gucy1b1<tm1.1Frb> MGI Mouse

premature death ( J:121321 )

• 90% of mice surviving past day 2 die between days 18 and 31 after birth coinciding with weaning and resulting change in diet

• when mice receive a fiber-free diet after weaning, survival improves greatly, but mice still die prematurely

neonatal lethality, incomplete penetrance ( J:121321 )

• 1 day postnatally, <25% of offspring are found to be homozygous, but Mendelian transmission numbers are found at E17.5-18.5

embryonic lethality between implantation and somite formation, complete penetrance ( J:121321 )

• 60% of homozygotes die within 2 days of birth

decreased body weight ( J:121321 )

• body weight reduced 40% relative to wild-type littermate controls

postnatal growth retardation ( J:121321 )

• mice show significant growth retardation, likely resulting from malnutrition

dilated esophagus ( J:121321 )

• mice with enlarged cecum may also display additional abnormalities to different degrees, such as enlarged esophagus

abnormal intestine morphology ( J:121321 )

• some mice have perforation of the intestinal wall

• some mice show intestinal necrosis

abnormal cecum morphology ( J:121321 )

• most mice have a grossly enlarged and dilated cecum

• in some animals, cecum is displaced from normal position

distended cecum ( J:121321 )

• grossly dilated in most mice

enlarged cecum ( J:121321 )

• grossly enlarged in most mice

enlarged stomach ( J:121321 )

• mice with enlarged cecum may also display additional abnormalities to different degrees, such as enlarged stomach

intestinal hypoperistalsis ( J:121321 )

abnormal intestinal transit time ( J:121321 )

• whole gut transit time is increased 3-fold over wild-type and heterozygous controls (>475 minutes vs ~150 minutes); when fed a fiber-free diet, transit time is still increased compared with controls (285 minutes vs ~165 minutes)

peritoneal inflammation ( J:121321 )

• some mice show peritonitis

abnormal systemic arterial blood pressure ( J:121321 )

• mice do not show decreased systolic blood pressure in response to glycerol trinitrate (GTN) whereas wild-type pressure is reduced

increased systemic arterial systolic blood pressure ( J:121321 )

• systolic blood pressure is significantly elevated compared to wild-type controls (130 mmHg vs 106 mmHg for controls)

abnormal vasodilation ( J:121321 )

• aortic rings from null mice do not relax in response to S-nitrosoglutathione or diethlyamine-NO, and other nitric oxide (NO) donor treatment after phenylephrine-induced contraction like wild-type aortic rings do

abnormal vasodilation ( J:121321 )

• aortic rings from null mice do not relax in response to S-nitrosoglutathione or diethlyamine-NO, and other nitric oxide (NO) donor treatment after phenylephrine-induced contraction like wild-type aortic rings do

intestinal hypoperistalsis ( J:121321 )

abnormal platelet activation ( J:121321 )

• collagen-induced aggregation is not inhibited in mutant platelets

• nitric oxide does not induce stimulation of PKG in mutant platelets as it does in wild-type platelets

dilated gallbladder ( J:121321 )

• mice with enlarged cecum may also display additional abnormalities to different degrees, such as a bloated gallbladder