Mouse Genome Informatics
hm
    Klkl/Klkl
involves: C3H/J * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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

growth/size
• 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
• after 3 weeks of age weight gain is greatly reduced

respiratory system
• lung volume is similar to wild-type but increased relative to body size
• enlarged alveolar ducts
• the number of alveoli contiguous with the alveolar ducts is reduced
• by 10 weeks of age normal alveolar structures are rarely seen
• by 10 weeks of age, calcified nodules are found attached to alveolar septa
• first seen at 4 weeks of age and becomes more prominent by 10 weeks
• longer expiratory time and reduced tidal volume; however respiratory rate and blood oxygen and carbon dioxide partial pressures are similar to wild-type
• higher dynamic compliance at tidal breathing

cardiovascular system
• mild to moderate Monckeberg type arteriosclerosis at 6 weeks of age but no appreciable calcification of the conduction system
• massive annular calcification at 6 weeks of age
• massive annular calcification at 6 weeks of age
• 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
• 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
• 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
• significant increase when normalized to body weight at 5 weeks of age
• at 5 weeks of age, males posses no visible subcutaneous, mesenteric, retroperitoneal, or epididymal fat
• brown adipose tissue contains smaller lipid droplets

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
• blood glucose is 76% of wild-type in 5-6 week old males fed ad libitum
• 56% of wild-type in 5-6 week old males
• in 5-6 week old males
• in 5-6 week old males

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

endocrine/exocrine glands
• reduction in beta cell specific staining
• reduced islet size

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
• apparent decrease in glycogen content

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

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

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