Phenotypes associated with this allele

• Allele Symbol: Pcsk1^tm1Dfs
• Allele Name: targeted mutation 1, Donald F Steiner
• Allele ID: MGI:2384741
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pcsk1^tm1Dfs/Pcsk1^tm1Dfs	involves: 129	MGI:3697747
hm2	Pcsk1^tm1Dfs/Pcsk1^tm1Dfs	involves: 129 * C57BL/6J	MGI:3054391
ht3	Pcsk1^tm1Dfs/Pcsk1^+	involves: 129 * C57BL/6J	MGI:3054394

Genotype
MGI:3697747

hm1

• Allelic Composition: Pcsk1^tm1Dfs/Pcsk1^tm1Dfs
• Genetic Background: involves: 129

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

homeostasis/metabolism

abnormal hormone level ( J:117652 )

• gastric ghrelin mRNA levels are elevated ~40% compared to controls

Genotype
MGI:3054391

hm2

• Allelic Composition: Pcsk1^tm1Dfs/Pcsk1^tm1Dfs
• Genetic Background: involves: 129 * C57BL/6J

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:184882 )

• in LPS-treated mice

postnatal lethality, incomplete penetrance ( J:78369 )

• high degree of postnatal lethality prior to 7 days of age

prenatal lethality, incomplete penetrance ( J:78369 )

• ratio of mutant homozygotes less than expected

immune system

enlarged spleen ( J:184882 )

abnormal T-helper 1 cell differentiation ( J:184882 )

• LPS treatment promotes TH1 differentiation

decreased T cell number ( J:184882 )

• slight in the spleen

decreased NK T cell number ( J:184882 )

• slight in the spleen

increased lymphocyte cell number ( J:184882 )

• in the splenic red pulp

abnormal peritoneal macrophage morphology ( J:184882 )

• following LPS treatment, peritoneal macrophage fail to exhibit a decrease in the number of peripheral vacuoles or an increase in phagolysosomal vacuoles unlike wild-type macrophage

• prior to LPS treatment, macrophage exhibit an increase in electron-dense vesicles compared with wild-type cells

• prior to and after LPS treatment, macrophage exhibit increased membrane projections compared with wild-type cells

abnormal spleen white pulp morphology ( J:184882 )

• white pulp is more concentrated in the middle of the spleen with fusion of white pulp nodes and some nodes in the periphery unlike in wild-type mice

intermingled spleen red and white pulp ( J:184882 )

abnormal spleen marginal zone morphology ( J:184882 )

increased circulating interferon-gamma level ( J:184882 )

• 30 times 8 hours after LPS treatment

increased circulating interleukin-1 beta level ( J:184882 )

• 5-fold 4 hours after LPS treatment

• 2 times 8 hours after LPS treatment

increased circulating interleukin-10 level ( J:184882 )

• 8 hours after LPS treatment

increased circulating interleukin-12 level ( J:184882 )

• 4 and 8 hours after LPS treatment

increased circulating interleukin-6 level ( J:184882 )

• 30 times 4 hours after LPS treatment

• 2-fold 8 hours after LPS treatment

increased circulating tumor necrosis factor level ( J:184882 )

• 8 times 4 hours after LPS treatment

decreased follicular dendritic cell number ( J:184882 )

• mostly disappeared from nodes and the marginal zone

increased interleukin-1 beta secretion ( J:184882 )

• 2.5-fold from PBS incubated macrophage

• however, macrophage stimulated with LPS for 4 hours exhibit normal IL1B secretion

increased susceptibility to endotoxin shock ( J:184882 )

• with increased lethality, decreased mean arterial blood pressure and increased cytokine production

digestive/alimentary system

chronic diarrhea ( J:78369 )

• chronic mild diarrhea with bulky, moist stools

growth/size/body

decreased body weight ( J:78369 )

• homozygotes can be identified three days after birth by smaller size

• by 6 weeks, body weight is 60% of wildtype

enlarged spleen ( J:184882 )

homeostasis/metabolism

hypoglycemia ( J:78369 )

• chronic

decreased circulating glucagon level ( J:78369 )

• lacks mature glucagon

decreased circulating insulin level ( J:78369 )

• hyperproinsulinemia

• reduced levels of mature insulin but normal glucose tolerance response

decreased circulating growth hormone level ( J:78369 )

• mature growth hormone releasing hormone levels are low or undetectable

increased circulating interferon-gamma level ( J:184882 )

• 30 times 8 hours after LPS treatment

increased circulating interleukin-1 beta level ( J:184882 )

• 5-fold 4 hours after LPS treatment

• 2 times 8 hours after LPS treatment

increased circulating interleukin-10 level ( J:184882 )

• 8 hours after LPS treatment

increased circulating interleukin-12 level ( J:184882 )

• 4 and 8 hours after LPS treatment

increased circulating interleukin-6 level ( J:184882 )

• 30 times 4 hours after LPS treatment

• 2-fold 8 hours after LPS treatment

increased circulating tumor necrosis factor level ( J:184882 )

• 8 times 4 hours after LPS treatment

decreased adrenocorticotropin level ( J:78369 )

• absence of mature ACTH in anterior and intermediate pituitary lobes

• POMC processing is impaired

• plasma corticosterone levels are normal

increased susceptibility to xenobiotic induced morbidity/mortality ( J:184882 )

• in LPS-treated mice

cardiovascular system

decreased mean systemic arterial blood pressure ( J:184882 )

• in LPS-treated mice

hematopoietic system

enlarged spleen ( J:184882 )

abnormal T-helper 1 cell differentiation ( J:184882 )

• LPS treatment promotes TH1 differentiation

decreased T cell number ( J:184882 )

• slight in the spleen

decreased NK T cell number ( J:184882 )

• slight in the spleen

increased lymphocyte cell number ( J:184882 )

• in the splenic red pulp

abnormal peritoneal macrophage morphology ( J:184882 )

• following LPS treatment, peritoneal macrophage fail to exhibit a decrease in the number of peripheral vacuoles or an increase in phagolysosomal vacuoles unlike wild-type macrophage

• prior to LPS treatment, macrophage exhibit an increase in electron-dense vesicles compared with wild-type cells

• prior to and after LPS treatment, macrophage exhibit increased membrane projections compared with wild-type cells

abnormal spleen white pulp morphology ( J:184882 )

• white pulp is more concentrated in the middle of the spleen with fusion of white pulp nodes and some nodes in the periphery unlike in wild-type mice

intermingled spleen red and white pulp ( J:184882 )

abnormal spleen marginal zone morphology ( J:184882 )

Genotype
MGI:3054394

ht3

• Allelic Composition: Pcsk1^tm1Dfs/Pcsk1⁺
• Genetic Background: involves: 129 * C57BL/6J

growth/size/body

obese ( J:78369 )

• mild obesity

homeostasis/metabolism

decreased circulating insulin level ( J:78369 )

• reduced levels of mature insulin

abnormal glucose tolerance ( J:78369 )

• prolonged glycemic response in response to glucose tolerance test