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Phenotypes Associated with This Genotype
Genotype
MGI:3653640
Allelic
Composition
Klkl/Klkl
Genetic
Background
involves: C3H/J * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Klkl mutation (0 available); any Kl mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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 (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 (J:102218)

growth/size/body
• 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 (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 (J:59775)
• after 3 weeks of age weight gain is greatly reduced (J:66078)
• after 3 weeks of age weight gain is greatly reduced (J:66078)

respiratory system
• lung volume is similar to wild-type but increased relative to body size (J:59775)
• lung volume is similar to wild-type but increased relative to body size (J:59775)
• enlarged alveolar ducts (J:59775)
• enlarged alveolar ducts (J:59775)
• the number of alveoli contiguous with the alveolar ducts is reduced (J:59775)
• by 10 weeks of age normal alveolar structures are rarely seen (J:59775)
• the number of alveoli contiguous with the alveolar ducts is reduced (J:59775)
• by 10 weeks of age normal alveolar structures are rarely seen (J:59775)
• by 10 weeks of age, calcified nodules are found attached to alveolar septa (J:59775)
• by 10 weeks of age, calcified nodules are found attached to alveolar septa (J:59775)
• first seen at 4 weeks of age and becomes more prominent by 10 weeks (J:59775)
• first seen at 4 weeks of age and becomes more prominent by 10 weeks (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 (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 (J:59775)
• higher dynamic compliance at tidal breathing (J:59775)
• higher dynamic compliance at tidal breathing (J:59775)

cardiovascular system
• mild to moderate Monckeberg type arteriosclerosis at 6 weeks of age but no appreciable calcification of the conduction system (J:102218)
• mild to moderate Monckeberg type arteriosclerosis at 6 weeks of age but no appreciable calcification of the conduction system (J:102218)
• massive annular calcification at 6 weeks of age (J:102218)
• massive annular calcification at 6 weeks of age (J:102218)
• massive annular calcification at 6 weeks of age (J:102218)
• massive annular calcification at 6 weeks of age (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 (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 (J:102218)
• after 1 hour of restraint stress RR interval increases in contrast RR interval decreases in wild-type mice (J:102218)
• application of 1 mg/kg atropine and 2 mg/kg propranolol produces a greater prolongation of the RR interval (J:102218)
• after 1 hour of restraint stress RR interval increases in contrast RR interval decreases in wild-type mice (J:102218)
• application of 1 mg/kg atropine and 2 mg/kg propranolol produces a greater prolongation of the RR interval (J:102218)
• after overdrive pacing sinus node recovery time and rate-corrected sinus node recovery time are significantly longer (J:102218)
• isoproterenol-induced shortening and acetylcholine-induced prolongation of the spontaneous cycle length is increased compared to wild-type mice (J:102218)
• after overdrive pacing sinus node recovery time and rate-corrected sinus node recovery time are significantly longer (J:102218)
• isoproterenol-induced shortening and acetylcholine-induced prolongation of the spontaneous cycle length is increased compared to wild-type mice (J:102218)

adipose tissue
• significant increase when normalized to body weight at 5 weeks of age (J:66078)
• significant increase when normalized to body weight at 5 weeks of age (J:66078)
• at 5 weeks of age, males posses no visible subcutaneous, mesenteric, retroperitoneal, or epididymal fat (J:66078)
• at 5 weeks of age, males posses no visible subcutaneous, mesenteric, retroperitoneal, or epididymal fat (J:66078)
• brown adipose tissue contains smaller lipid droplets (J:66078)
• brown adipose tissue contains smaller lipid droplets (J:66078)

homeostasis/metabolism
• about a 2-fold increase in baseline levels; however levels decrease slightly during stress unlike in wild-type mice where levels increase dramatically (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 (J:102218)
• blood glucose is 76% of wild-type in 5-6 week old males fed ad libitum (J:66078)
• blood glucose is 76% of wild-type in 5-6 week old males fed ad libitum (J:66078)
• 56% of wild-type in 5-6 week old males (J:66078)
• 56% of wild-type in 5-6 week old males (J:66078)
• in 5-6 week old males (J:66078)
• in 5-6 week old males (J:66078)
• in 5-6 week old males (J:66078)
• in 5-6 week old males (J:66078)

skeleton
• 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 (J:56666)
• however, in vitro bone resorption per osteoclast is similar to wild-type (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 (J:56666)
• however, in vitro bone resorption per osteoclast is similar to wild-type (J:56666)
• bone mineral density is reduced in the mid portion (diaphysis) of the tibia and femur but increased in the distal portion (metaphysis) (J:56666)
• bone mineral density is reduced in the mid portion (diaphysis) of the tibia and femur but increased in the distal portion (metaphysis) (J:56666)
• at 7 weeks of age, overall bone mineral densities of the tibia and femur are reduced by 12% and 5%, respectively (J:56666)
• at 7 weeks of age, overall bone mineral densities of the tibia and femur are reduced by 12% and 5%, respectively (J:56666)
• in the tibia and femur at 7 weeks of age (J:56666)
• at 7 weeks of age, cortical bone thickness is reduced by about 40% in the tibia (J:56666)
• in the tibia and femur at 7 weeks of age (J:56666)
• at 7 weeks of age, cortical bone thickness is reduced by about 40% in the tibia (J:56666)
• osteoblast surface per bone surface is reduced (J:56666)
• osteoblast surface per bone surface is reduced (J:56666)
• 3-fold fewer osteoblast colony forming units are found in marrow cells from 4 and 7 week old mice (J:56666)
• 3-fold fewer osteoblast colony forming units are found in marrow cells from 4 and 7 week old mice (J:56666)
• increased density and length of trabecular at the metaphysis of the tibia and femur (J:56666)
• at 7 weeks of age in the tibia, trabecular bone volume and thickness are increased by 100% and 30%, respectively (J:56666)
• increased density and length of trabecular at the metaphysis of the tibia and femur (J:56666)
• at 7 weeks of age in the tibia, trabecular bone volume and thickness are increased by 100% and 30%, respectively (J:56666)
• bone formation and bone resorption rates are reduced by about 80-90% and 60% respectively (J:56666)
• bone formation and bone resorption rates are reduced by about 80-90% and 60% respectively (J:56666)
• osteoblast cells from 5-6 day old mice, but not embryos, have lower alkaline phosphatase activity and decreased matrix nodule formation (J:56666)
• osteoblast cells from 5-6 day old mice, but not embryos, have lower alkaline phosphatase activity and decreased matrix nodule formation (J:56666)

endocrine/exocrine glands
• reduction in beta cell specific staining (J:66078)
• reduction in beta cell specific staining (J:66078)
• reduced islet size (J:66078)
• reduced islet size (J:66078)

liver/biliary system
• 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 (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 (J:66078)
• apparent decrease in glycogen content (J:66078)
• apparent decrease in glycogen content (J:66078)

hematopoietic system
• however, in vitro bone resorption per osteoclast is similar to wild-type (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 (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 (J:56666)
• however, in vitro bone resorption per osteoclast is similar to wild-type (J:56666)

immune system
• 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 (J:56666)
• however, in vitro bone resorption per osteoclast is similar to wild-type (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 (J:56666)
• however, in vitro bone resorption per osteoclast is similar to wild-type (J:56666)

Mouse Models of Human Disease
OMIM ID Ref(s)
Klotho; KL 604824 J:102218


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory