Phenotypes associated with this allele

• Allele Symbol: Mff^{Gt(AZ0438)Wtsi}
• Allele Name: gene trap AZ0438, Wellcome Trust Sanger Institute
• Allele ID: MGI:3857630
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mff^Gt(AZ0438)Wtsi/Mff^Gt(AZ0438)Wtsi	involves: 129P2/OlaHsd * C57BL/6	MGI:6156141
hm2	Mff^Gt(AZ0438)Wtsi/Mff^Gt(AZ0438)Wtsi	involves: 129P2/OlaHsd * C57BL/6J	MGI:7261372
cx3	Gt(ROSA)26Sor^tm1.1(CAG-COX8A/Dendra2)Dcc/Gt(ROSA)26Sor^+ Mff^Gt(AZ0438)Wtsi/Mff^Gt(AZ0438)Wtsi	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * C57BL/6J	MGI:7261374

Genotype
MGI:6156141

hm1

• Allelic Composition: Mff^{Gt(AZ0438)Wtsi}/Mff^{Gt(AZ0438)Wtsi}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

cardiovascular system

decreased myocardial infarct size ( J:255071 )

• decreased CMEC (cardiac microcirculation endothelial cell) mitochondrial apoptotic cell death compared to wild-type after surgical induction of ischemia/reperfusion (IR) injury (30 min. ischemia followed by 2 hours reperfusion)

cellular

decreased apoptosis ( J:255071 )

• compared to wild-type after surgical induction of ischemia/reperfusion (IR) injury (30 min. ischemia followed by 2 hours reperfusion)

homeostasis/metabolism

decreased myocardial infarct size ( J:255071 )

• decreased CMEC (cardiac microcirculation endothelial cell) mitochondrial apoptotic cell death compared to wild-type after surgical induction of ischemia/reperfusion (IR) injury (30 min. ischemia followed by 2 hours reperfusion)

mortality/aging

abnormal induced morbidity/mortality ( J:255071 )

• compared to wild-type after surgical induction of ischemia/reperfusion (IR) injury (30 min. ischemia followed by 2 hours reperfusion)

• increase in phosphor-endothelial nitic oxide synthase levels in cardiac microvessels

• normal red blood cell shape

• reduced levels of Icam1 and Vcam1 on surface of cardiac microcirculation endothelial cells (CMECs)

• reversal of F4/80+ cell accumulation in myocardial tissue

• normal morphology of cardiac microcirculation endothelial cells (CMECs) and their mitochondria

• increased expression of Cdh5 in CMECs

• decreased CMEC mitochondrial apoptotic cell death

Genotype
MGI:7261372

hm2

• Allelic Composition: Mff^{Gt(AZ0438)Wtsi}/Mff^{Gt(AZ0438)Wtsi}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

reproductive system

abnormal sperm midpiece morphology ( J:301349 )

♂ • caudal epididymidal sperm often show indentations in the midpiece as well as kinking at the distal end of the midpiece

abnormal sperm mitochondrial sheath morphology ( J:301349 )

♂ • abnormally enlarged mitochondria are poorly recruited to the sperm midpiece and/or fail to properly wrap around the axoneme, resulting in disjointed mitochondrial sheaths

cellular

abnormal sperm midpiece morphology ( J:301349 )

♂ • caudal epididymidal sperm often show indentations in the midpiece as well as kinking at the distal end of the midpiece

abnormal sperm mitochondrial sheath morphology ( J:301349 )

♂ • abnormally enlarged mitochondria are poorly recruited to the sperm midpiece and/or fail to properly wrap around the axoneme, resulting in disjointed mitochondrial sheaths

abnormal mitochondrial morphology ( J:301349 )

♂ • epididymidal sperm exhibit disjointed mitochondrial sheaths with high variation in mitochondrial morphology

♂ • 3D electron tomography of longitudinal sections of epididymal sperm showed wider mitochondria and large empty spaces where mitochondria should be found

♂ • similar mitochondrial defects are seen in testicular spermatozoa, prior to their release into the epididymides

♂ • TEM analysis of round spermatids in testis sections showed that >20% of mitochondria have an elongated and highly constricted morphology, suggesting a fission defect; in contrast, most wild-type round spermatid mitochondria are small and fragmented

♂ • ~80% of round spermatids contain one or more constricted mitochondria

decreased mitochondrial number ( J:301349 )

♂ • in longitudinal sections of sperm midpieces, mitochondria are too sparse to form a uniform sheath

increased mitochondrial size ( J:301349 )

♂ • in longitudinal sections of sperm midpieces, mitochondria have increased transverse diameters

♂ • in transverse sections, mitochondria are also slightly elongated relative to controls

dilated mitochondrion ( J:301349 )

♂ • in longitudinal sections of sperm midpieces, mitochondria appear highly swollen

abnormal mitochondrial ATP synthesis coupled electron transport ( J:301349 )

♂ • sperm midpiece mitochondria show reduced COX (cytochrome c oxidase) staining and increased SDH (succinate dehydrogenase) staining, indicating decreased respiratory chain complex IV activity

Genotype
MGI:7261374

cx3

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(CAG-COX8A/Dendra2)Dcc}/Gt(ROSA)26Sor⁺; Mff^{Gt(AZ0438)Wtsi}/Mff^{Gt(AZ0438)Wtsi}
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * C57BL/6J

reproductive system

abnormal sperm connecting piece morphology ( J:301349 )

♂ • >5% of caudal epididymidal sperm contain kinks in the neck

abnormal sperm midpiece morphology ( J:301349 )

♂ • >15% of caudal epididymidal sperm contain kinks in the midpiece

abnormal sperm mitochondrial sheath morphology ( J:301349 )

♂ • caudal epididymidal sperm show disjointed mitochondrial sheaths with gaps between adjacent organelles

abnormal sperm principal piece morphology ( J:301349 )

♂ • >40% of caudal epididymidal sperm contain kinks in the principal piece

kinked sperm flagellum ( J:301349 )

♂ • >60% of caudal epididymidal sperm contain kinks in the midpiece, principal piece or neck

abnormal spermatid morphology ( J:301349 )

♂ • most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented

asthenozoospermia ( J:301349 )

♂ • caudal epididymidal sperm are significantly less motile than wild-type sperm

decreased fertilization frequency ( J:301349 )

♂ • in an in vitro fertilization assay, cauda epididymidal sperm failed to fertilize any oocytes

cellular

abnormal sperm connecting piece morphology ( J:301349 )

♂ • >5% of caudal epididymidal sperm contain kinks in the neck

abnormal sperm midpiece morphology ( J:301349 )

♂ • >15% of caudal epididymidal sperm contain kinks in the midpiece

abnormal sperm mitochondrial sheath morphology ( J:301349 )

♂ • caudal epididymidal sperm show disjointed mitochondrial sheaths with gaps between adjacent organelles

abnormal sperm principal piece morphology ( J:301349 )

♂ • >40% of caudal epididymidal sperm contain kinks in the principal piece

kinked sperm flagellum ( J:301349 )

♂ • >60% of caudal epididymidal sperm contain kinks in the midpiece, principal piece or neck

abnormal spermatid morphology ( J:301349 )

♂ • most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented

abnormal mitochondrial morphology ( J:301349 )

♂ • most round and elongating spermatids contain tubular mitochondria, unlike in wild-type spermatids where mitochondria are almost always fragmented

decreased mitochondrial number ( J:301349 )

♂ • total mito-Dendra2 fluorescence is markedly reduced in the midpiece of epididymidal sperm

asthenozoospermia ( J:301349 )

♂ • caudal epididymidal sperm are significantly less motile than wild-type sperm