Phenotypes Associated with This Genotype

Genotype
MGI:3653640

• Allelic Composition: Kl^kl/Kl^kl
• Genetic Background: involves: C3H/J * C57BL/6J

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

limbs/digits/tail

decreased femur compact bone thickness ( J:56666 )

• reduced cortical bone thickness in the femur at 7 weeks of age

cellular

abnormal osteoblast physiology ( J:56666 )

• osteoblast cells from 5-6 day old mice, but not embryos, have lower alkaline phosphatase activity and decreased matrix nodule formation

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:102218 )

• at 6 weeks of age during a 20 hour restraint challenge the survival rate decreases progressively with 20 of 30 male mice dead by the end of the experiment, compared to 100% survival of wild-type mice

growth/size/body

decreased body length ( J:59775 )

• at 6-8 weeks of age, mean body length is 68.3 +/- 4.7 mm compared to 91.5 +/- 1.0 mm in wild-type mice

postnatal growth retardation ( J:66078 )

• after 3 weeks of age weight gain is greatly reduced

respiratory system

abnormal lung morphology ( J:59775 )

• lung volume is similar to wild-type but increased relative to body size

dilated pulmonary alveolar duct ( J:59775 )

• enlarged alveolar ducts

abnormal pulmonary alveolus morphology ( J:59775 )

• the number of alveoli contiguous with the alveolar ducts is reduced

• by 10 weeks of age normal alveolar structures are rarely seen

abnormal pulmonary interalveolar septum morphology ( J:59775 )

• by 10 weeks of age, calcified nodules are found attached to alveolar septa

emphysema ( J:59775 )

• first seen at 4 weeks of age and becomes more prominent by 10 weeks

decreased tidal volume ( J:59775 )

abnormal respiratory mechanics ( J:59775 )

• longer expiratory time and reduced tidal volume; however respiratory rate and blood oxygen and carbon dioxide partial pressures are similar to wild-type

increased lung compliance ( J:59775 )

• higher dynamic compliance at tidal breathing

cardiovascular system

arteriosclerosis ( J:102218 )

• mild to moderate Monckeberg type arteriosclerosis at 6 weeks of age but no appreciable calcification of the conduction system

abnormal heart valve morphology ( J:102218 )

calcified mitral valve annulus ( J:102218 )

• massive annular calcification at 6 weeks of age

calcified aortic valve annulus ( J:102218 )

• massive annular calcification at 6 weeks of age

abnormal cardiovascular system physiology ( J:102218 )

decreased heart rate ( J:102218 )

• after 4 hours of restraint bradyarrhythmias resulting from sinoatrial node dysfunction are seen; however, no supraventricular brady/tachyarrhythmias, atrial fibrilations, or ventricular tachyarrhythmias are seen

prolonged RR interval ( J:102218 )

• after 1 hour of restraint stress RR interval increases in contrast RR interval decreases in wild-type mice

• application of 1 mg/kg atropine and 2 mg/kg propranolol produces a greater prolongation of the RR interval

abnormal sinoatrial node conduction ( J:102218 )

• after overdrive pacing sinus node recovery time and rate-corrected sinus node recovery time are significantly longer

• isoproterenol-induced shortening and acetylcholine-induced prolongation of the spontaneous cycle length is increased compared to wild-type mice

adipose tissue

increased brown adipose tissue amount ( J:66078 )

• significant increase when normalized to body weight at 5 weeks of age

decreased white adipose tissue amount ( J:66078 )

• at 5 weeks of age, males posses no visible subcutaneous, mesenteric, retroperitoneal, or epididymal fat

decreased brown fat cell lipid droplet size ( J:66078 )

• brown adipose tissue contains smaller lipid droplets

homeostasis/metabolism

increased circulating noradrenaline level ( J:102218 )

• about a 2-fold increase in baseline levels; however levels decrease slightly during stress unlike in wild-type mice where levels increase dramatically

decreased body temperature ( J:66078 )

abnormal glucose homeostasis ( J:66078 )

hypoglycemia ( J:66078 )

• blood glucose is 76% of wild-type in 5-6 week old males fed ad libitum

decreased circulating insulin level ( J:66078 )

• 56% of wild-type in 5-6 week old males

improved glucose tolerance ( J:66078 )

• in 5-6 week old males

increased insulin sensitivity ( J:66078 )

• in 5-6 week old males

skeleton

abnormal osteoblast physiology ( J:56666 )

• osteoblast cells from 5-6 day old mice, but not embryos, have lower alkaline phosphatase activity and decreased matrix nodule formation

abnormal osteoclast morphology ( J:56666 )

• decreased osteoclast surface area per bone surface area and number of osteoclasts produced in vitro independent of the source of the osteoblast cells used in the culture

• however, in vitro bone resorption per osteoclast is similar to wild-type

abnormal bone mineral density ( J:56666 )

• bone mineral density is reduced in the mid portion (diaphysis) of the tibia and femur but increased in the distal portion (metaphysis)

decreased bone mineral density ( J:56666 )

• at 7 weeks of age, overall bone mineral density of the tibia is reduced by 12%

decreased bone mineral density of femur ( J:56666 )

• at 7 weeks of age, overall bone mineral densiy of the femur is reduced by 5%

decreased compact bone thickness ( J:56666 )

• at 7 weeks of age, cortical bone thickness is reduced by about 40% in the tibia

decreased femur compact bone thickness ( J:56666 )

• reduced cortical bone thickness in the femur at 7 weeks of age

abnormal osteoblast morphology ( J:56666 )

• osteoblast surface per bone surface is reduced

decreased osteoblast cell number ( J:56666 )

• 3-fold fewer osteoblast colony forming units are found in marrow cells from 4 and 7 week old mice

abnormal trabecular bone morphology ( J:56666 )

• increased density and length of trabecular at the metaphysis of the tibia and femur

• at 7 weeks of age in the tibia, trabecular bone volume and thickness are increased by 100% and 30%, respectively

decreased bone ossification ( J:56666 )

• bone formation rate is reduced by about 80-90%

decreased bone resorption ( J:56666 )

• bone resorption rate is reduced by about 60%

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:66078 )

• reduction in beta cell specific staining

small pancreatic islets ( J:66078 )

• reduced islet size

liver/biliary system

decreased liver weight ( J:66078 )

• at 5 weeks of age, slight but significant decrease in liver weight when normalized to body weight; however, kidney and pancreas weights are proportional to body size

abnormal liver physiology ( J:66078 )

• apparent decrease in glycogen content

hematopoietic system

abnormal osteoclast morphology ( J:56666 )

• decreased osteoclast surface area per bone surface area and number of osteoclasts produced in vitro independent of the source of the osteoblast cells used in the culture

• however, in vitro bone resorption per osteoclast is similar to wild-type

immune system

abnormal osteoclast morphology ( J:56666 )

• decreased osteoclast surface area per bone surface area and number of osteoclasts produced in vitro independent of the source of the osteoblast cells used in the culture

• however, in vitro bone resorption per osteoclast is similar to wild-type