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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Leprdb-5J
diabetes 5 Jackson
MGI:2683234
Summary 3 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Leprdb-5J/Leprdb-5J NOD/ShiLtJ-Leprdb-5J/LtJ MGI:2684204
hm2
Leprdb-5J/Leprdb-5J NOD/ShiLt-Leprdb-5J MGI:3699232
ht3
Leprdb/Leprdb-5J involves: C57BLKS/J * NOD/ShiLtJ MGI:3699233


Genotype
MGI:2684204
hm1
Allelic
Composition
Leprdb-5J/Leprdb-5J
Genetic
Background
NOD/ShiLtJ-Leprdb-5J/LtJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb-5J mutation (1 available); any Lepr mutation (122 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• beta-degranulation in the islets of Langerhans

growth/size/body
• both males and females are obese by weaning age

homeostasis/metabolism
• age of onset by 5 weeks




Genotype
MGI:3699232
hm2
Allelic
Composition
Leprdb-5J/Leprdb-5J
Genetic
Background
NOD/ShiLt-Leprdb-5J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb-5J mutation (1 available); any Lepr mutation (122 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 3/6 males showing weight loss with severe hyperglycemia die by 41-49 weeks of age
• mice with juvenile-onset hyperglycemia did not require insulin therapy to survive to >39 weeks, whereas wild-type NOD littermates developed adult onset hyperglycemia, rapidly lost weight, and were euthanized

growth/size/body
• 35.3% (6/17) homozygous males show a persistent decrease in weight beginning at 7-9 weeks and continuing to 39 weeks of age
• within 1 week of weaning, mice gain 6-10 grams more than wild-type littermates
• females show rapid weight gain up ~15 weeks of age to a ~stable weight of 40 grams
• males also show marked weight gain after weaning; in 64.7% of males (11/17), postpubertal (from 7 weeks of age) weight gain continues

homeostasis/metabolism
N
• plasmacorticosterone levels in mutants and NOD controls are similar
• hyperglycemia in all females and subset of males remits to normoglycemia with increasing age, while lean littermates show progression to type I diabetes
• 4/11 males showing maintained elevated body weight become normoglycemic (glucose 145 mg/dl at 39 weeks); remaining 7 males in this group are still hyperglycemic but exhibit lower mean blood glucose level (386 mg/dl) at 39 weeks
• develops in most obese mice withing 2 weeks of weaning
• the males (6/17) showing decrease in body weight display severe hyperglycemia (glucose 581 mg/dl at 39 weeks)
• by 5-7 weeks of age, 4/5 females and 11/17 males are hyperglycemic (glucose >200 mg/dl) and most remain hyperglycemic through the peripubertal period (253-686 mg/dl at 13 weeks)
• levels increase markedly above lean controls with age
• females remitting to normoglycemia still exhibit elevated insulin levels; males showing weight loss display reduced insulin levels (~nondiabetic control), while males maintaining elevated weight still show elevated levels
• levels increase markedly above lean controls with age
• females remitting to normoglycemia still exhibit elevated leptin levels

endocrine/exocrine glands
• animals that maintained high body weight with or without remission from intermediate levels of hyperglycemia have extremely hyperplastic islets with well-granulated beta cells; islets display peri-insulitis
• males exhibiting unrestrained hyperglycemia and weight loss have islets reduced in size and number of granulated beta cells, but showing minimal intraislet insulitis
• islets are normal-sized with markedly degranulated beta cells
• perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed

behavior/neurological
• early weight gain is associated with hyperphagia; at 5 weeks, mice consume twice as much as lean controls

adipose tissue
• at 15 weeks, females have 40.5% carcass fat vs 19.9% in lean littermates; males show 33% body fat vs 14.7% in lean males

immune system
• perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed
• CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%)
• beta cell autoreactive CD8+ T cell clonotypes are decreased in mutants compared to NOD controls; IGRP and insulin-reactive CD8+ clonotypes are 5.7- and 1.7-fold lower in spleens of female mutants compared to controls

hematopoietic system
• CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%)
• beta cell autoreactive CD8+ T cell clonotypes are decreased in mutants compared to NOD controls; IGRP and insulin-reactive CD8+ clonotypes are 5.7- and 1.7-fold lower in spleens of female mutants compared to controls




Genotype
MGI:3699233
ht3
Allelic
Composition
Leprdb/Leprdb-5J
Genetic
Background
involves: C57BLKS/J * NOD/ShiLtJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (17 available); any Lepr mutation (122 available)
Leprdb-5J mutation (1 available); any Lepr mutation (122 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 25% of offspring exhibit obesity





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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory