Lepr<db-5J> Spontaneous Allele Detail MGI Mouse (MGI:2683234)

Lepr^db-5J
Spontaneous Allele Detail

Nomenclature

Symbol:	Lepr^db-5J
Name:	leptin receptor; diabetes 5 Jackson
MGI ID:	MGI:2683234
Gene:	Lepr Location: Chr4:101390009-101487957 bp, + strand Genetic Position: Chr4, 46.7 cM

Mutation
origin

Strain of Origin:

NOD/ShiLtJ

Mutation
description

Allele Type:	Spontaneous
Mutation:	Single point mutation
	A G to T transversion mutation was found in exon 13 effecting a glycine640valine change in the receptor. (J:87061)
Inheritance:	Recessive

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Lepr Mutation:	21 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	ht3
adipose tissue		√
increased percent body fat		√
		hm1	hm2	ht3
behavior/neurological		√
polyphagia		√
		hm1	hm2	ht3
digestive/alimentary system		√	√
abnormal pancreatic islet morphology		√
degranulated pancreatic beta cells		√	√
pancreatic islet hyperplasia			√
pancreas inflammation		√
periinsulitis		√
		hm1	hm2	ht3
endocrine/exocrine glands		√	√
abnormal pancreatic islet morphology		√
degranulated pancreatic beta cells		√	√
pancreatic islet hyperplasia			√
pancreas inflammation		√
periinsulitis		√
		hm1	hm2	ht3
growth/size		√	√	√
weight loss		√
increased weight gain		√
obese			√	√
		hm1	hm2	ht3
hematopoietic system		√
abnormal CD4-positive T cell morphology		√
abnormal CD8-positive T cell morphology		√
		hm1	hm2	ht3
homeostasis/metabolism		√	√
homeostasis/metabolism phenotype		N
abnormal circulating glucose level		√
hyperglycemia		√	√
increased circulating insulin level		√	√
increased circulating leptin level		√
		hm1	hm2	ht3
immune system		√
pancreas inflammation		√
periinsulitis		√
abnormal CD4-positive T cell morphology		√
abnormal CD8-positive T cell morphology		√
		hm1	hm2	ht3
life span/aging		√
premature death		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Lepr^db-5J/Lepr^db-5J	NOD/ShiLt-Lepr^db-5J
life span/aging premature death (J:118305) 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 weight loss (J:118305) 35.3% (6/17) homozygous males show a persistent decrease in weight beginning at 7-9 weeks and continuing to 39 weeks of age increased weight gain (J:118305) 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 homeostasis/metabolism phenotype (J:118304) plasmacorticosterone levels in mutants and NOD controls are similar abnormal circulating glucose level (J:118305) 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 hyperglycemia (J:118305) 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) increased circulating insulin level (J:118305) 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 increased circulating leptin level (J:118305) levels increase markedly above lean controls with age females remitting to normoglycemia still exhibit elevated leptin levels endocrine/exocrine glands abnormal pancreatic islet morphology (J:118305) 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 degranulated pancreatic beta cells (J:118305) islets are normal-sized with markedly degranulated beta cells pancreas inflammation (J:118305) perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed periinsulitis (J:118305) digestive/alimentary system abnormal pancreatic islet morphology (J:118305) 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 degranulated pancreatic beta cells (J:118305) islets are normal-sized with markedly degranulated beta cells pancreas inflammation (J:118305) perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed periinsulitis (J:118305) behavior/neurological polyphagia (J:118305) early weight gain is associated with hyperphagia; at 5 weeks, mice consume twice as much as lean controls adipose tissue increased percent body fat (J:118305) 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 pancreas inflammation (J:118305) perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed periinsulitis (J:118305) abnormal CD4-positive T cell morphology (J:118304) CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%) abnormal CD8-positive T cell morphology (J:118304) 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 abnormal CD4-positive T cell morphology (J:118304) CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%) abnormal CD8-positive T cell morphology (J:118304) 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	Allelic Composition	Genetic Background
hm2	Lepr^db-5J/Lepr^db-5J	NOD/ShiLtJ
digestive/alimentary system degranulated pancreatic beta cells (J:87061) beta-degranulation in the islets of Langerhans pancreatic islet hyperplasia (J:87061) endocrine/exocrine glands degranulated pancreatic beta cells (J:87061) beta-degranulation in the islets of Langerhans pancreatic islet hyperplasia (J:87061) growth/size obese (J:87061) both males and females are obese by weaning age homeostasis/metabolism hyperglycemia (J:87061) age of onset by 5 weeks increased circulating insulin level (J:87061)
Genotype	Allelic Composition	Genetic Background
ht3	Lepr^db/Lepr^db-5J	involves: C57BLKS/J * NOD/ShiLtJ
growth/size obese (J:118305) 25% of offspring exhibit obesity

References

Original:	J:87061 Leiter EH et al., "Leptin receptor deficiency in NOD/LtJ mice produces a type 2 diadetes syndrome with suppressed autoimmunity" MGI Direct Data Submission 2004;():
All:	3 reference(s)

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