Phenotypes Associated with This Genotype

Genotype
MGI:2174985

• Allelic Composition: Pik3r1^tm1Tka/Pik3r1^tm1Tka
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:52228 )

• 80% of mice die within 10 weeks of birth due to bacterial infection

immune system

decreased pro-B cell number ( J:52228 )

• B220+CD43+ pro-B cells in the bone marrow are reduced compared to in wild-type mice

decreased B cell number ( J:52228 )

• the number of IgM+CD5+Ly-1 B cells in the peritoneal cavity is reduced compared to in wild-type mice

decreased mature B cell number ( J:52228 )

• the number of mature B220+IgM+ B cells in the spleen, bone marrow an lymph nodes is less than half of wild-type

• IgM^loIgD^hi mature B cells in the spleen is reduced

decreased pre-B cell number ( J:52228 )

• B220+CD43- pre-B cells in the bone marrow are reduced compared to in wild-type mice

abnormal B cell physiology ( J:113491 )

• entry into the cell cycle and, by consequence proliferation, of B cells in response to anti-IgM antibodies is delayed compared to in wild-type mice

• in response to treatment with anti-IgM antibodies, apoptosis of B cells increased unlike in wild-type mice

decreased B cell proliferation ( J:52228 , J:113491 )

• B cell proliferation is impaired in response to LPS, anti-IgM, and anti-CD40 treatment (J:52228)

• however, proliferation in response to a phorbol ester and ionomycin is normal (J:52228)

abnormal humoral immune response ( J:52228 )

• mice do not produce anti-DNP antibodies when stimulated with DNP-Ficoll

• however, mice produce anti-DNP antibodies when stimulated with DNP-KLH

increased susceptibility to bacterial infection ( J:52228 )

• 80% of mice die within 10 weeks of birth due to bacterial infection

homeostasis/metabolism

decreased circulating glucose level ( J:52576 )

• 114+/-5 mg/dl compared to 140+/-4 mg/dl in wild-type mice when loaded with glucose, mice exhibit a smaller increase in glucose levels

hypoglycemia ( J:52576 )

• when loaded with insulin

decreased circulating insulin level ( J:52576 )

• when loaded with glucose, mice exhibit a smaller increase in insulin levels

increased insulin sensitivity ( J:52576 )

adipose tissue

increased adipocyte glucose uptake ( J:52576 )

• C14 glucose uptake in adipocytes is increased 199% and 159% compared to wild-type mice at basal and 10 nM insulin, respectively

• 2-3-O-methylglucose uptake is increased 2- to 3-fold compared to in wild-type mice at physiological concentrations of insulin (0.1-1.0 nM)

muscle

increased skeletal muscle cell glucose uptake ( J:52576 )

• 2-deoxy-glucose uptake is in the soleus muscle is increased 133% and 140% compared to wild-type at basal and 10 nM insulin, respectively

hematopoietic system

decreased pro-B cell number ( J:52228 )

• B220+CD43+ pro-B cells in the bone marrow are reduced compared to in wild-type mice

decreased B cell number ( J:52228 )

• the number of IgM+CD5+Ly-1 B cells in the peritoneal cavity is reduced compared to in wild-type mice

decreased mature B cell number ( J:52228 )

• the number of mature B220+IgM+ B cells in the spleen, bone marrow an lymph nodes is less than half of wild-type

• IgM^loIgD^hi mature B cells in the spleen is reduced

decreased pre-B cell number ( J:52228 )

• B220+CD43- pre-B cells in the bone marrow are reduced compared to in wild-type mice

abnormal B cell physiology ( J:113491 )

• entry into the cell cycle and, by consequence proliferation, of B cells in response to anti-IgM antibodies is delayed compared to in wild-type mice

• in response to treatment with anti-IgM antibodies, apoptosis of B cells increased unlike in wild-type mice

decreased B cell proliferation ( J:52228 , J:113491 )

• B cell proliferation is impaired in response to LPS, anti-IgM, and anti-CD40 treatment (J:52228)

• however, proliferation in response to a phorbol ester and ionomycin is normal (J:52228)

cellular

increased adipocyte glucose uptake ( J:52576 )

• C14 glucose uptake in adipocytes is increased 199% and 159% compared to wild-type mice at basal and 10 nM insulin, respectively

• 2-3-O-methylglucose uptake is increased 2- to 3-fold compared to in wild-type mice at physiological concentrations of insulin (0.1-1.0 nM)

decreased B cell proliferation ( J:52228 , J:113491 )

• however, proliferation in response to a phorbol ester and ionomycin is normal (J:52228)

• B cell proliferation is impaired in response to LPS, anti-IgM, and anti-CD40 treatment (J:52228)

increased skeletal muscle cell glucose uptake ( J:52576 )

• 2-deoxy-glucose uptake is in the soleus muscle is increased 133% and 140% compared to wild-type at basal and 10 nM insulin, respectively

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
X-linked agammaglobulinemia		DOID:14179	OMIM:300755	J:52228